92 results on '"Gallo, Richard L"'
Search Results
52. Toll-like receptor 3 activation is required for normal skin barrier repair following UV damage.
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Borkowski, Andrew W, Kuo, I-Hsin, Bernard, Jamie J, Yoshida, Takeshi, Williams, Michael R, Hung, Nai-Jung, Yu, Benjamin D, Beck, Lisa A, and Gallo, Richard L
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Tight Junctions ,Keratinocytes ,Skin ,Animals ,Mice ,Inbred C57BL ,Mice ,Poly I-C ,Cytokines ,Ultraviolet Rays ,Permeability ,Female ,Male ,Toll-Like Receptor 3 ,Inbred C57BL ,Clinical Sciences ,Oncology and Carcinogenesis ,Dermatology & Venereal Diseases - Abstract
UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA triggers inflammation in the skin following UV damage. Recently, TLR3 activation was also shown to aid wound repair and increase the expression of genes associated with permeability barrier repair. Here, we sought to test whether skin barrier repair after UVB damage is dependent on the activation of TLR3. We observed that multiple ncRNAs induced expression of skin barrier repair genes, that the TLR3 ligand Poly (I:C) also induced expression and function of tight junctions, and that the ncRNA U1 acts in a TLR3-dependent manner to induce expression of skin barrier repair genes. These observations were shown to have functional relevance as Tlr3-/- mice displayed a delay in skin barrier repair following UVB damage. Combined, these data further validate the conclusion that recognition of endogenous RNA by TLR3 is an important step in the program of skin barrier repair.
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- 2015
53. Vaccinia Virus Binds to the Scavenger Receptor MARCO on the Surface of Keratinocytes
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MacLeod, Daniel T, Nakatsuji, Teruaki, Wang, Zhenping, di Nardo, Anna, and Gallo, Richard L
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Prevention ,Biodefense ,Clinical Research ,Vaccine Related ,Aetiology ,2.1 Biological and endogenous factors ,Skin ,Animals ,Cells ,Cultured ,Dermatitis ,Atopic ,Humans ,Keratinocytes ,Mice ,Inbred C57BL ,Mice ,Knockout ,Protein Binding ,Receptors ,Immunologic ,Receptors ,Scavenger ,Smallpox Vaccine ,Vaccinia ,Vaccinia virus ,Viral Vaccines ,Clinical Sciences ,Oncology and Carcinogenesis ,Dermatology & Venereal Diseases - Abstract
Patients with altered skin immunity, such as individuals with atopic dermatitis (AD), can have a life-threatening disruption of the epidermis known as eczema vaccinatum after vaccinia virus (VV) infection of the skin. Here, we sought to better understand the mechanism(s) by which VV associates with keratinocytes. The class A scavenger receptor known as MARCO (macrophage receptor with collagenous structure) is expressed on human and mouse keratinocytes and found to be abundantly expressed in the skin of patients with AD. VV bound directly to MARCO, and overexpression of MARCO increased susceptibility to VV infection. Furthermore, ligands with affinity for MARCO, or excess soluble MARCO, competitively inhibited VV infection. These findings indicate that MARCO promotes VV infection and highlights potential new therapeutic strategies for prevention of VV infection in the skin.
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- 2015
54. Mast cells are key mediators of cathelicidin-initiated skin inflammation in rosacea.
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Muto, Yumiko, Wang, Zhenping, Vanderberghe, Matthieu, Two, Aimee, Gallo, Richard L, and Di Nardo, Anna
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Mast Cells ,Keratinocytes ,Skin ,Animals ,Mice ,Inbred C57BL ,Humans ,Mice ,Rosacea ,Disease Models ,Animal ,Inflammation ,Antimicrobial Cationic Peptides ,Interleukin-6 ,Matrix Metalloproteinase 9 ,Tryptases ,Chymases ,Disease Models ,Animal ,Inbred C57BL ,Clinical Sciences ,Oncology and Carcinogenesis ,Dermatology & Venereal Diseases - Abstract
Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers are increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cause vasodilation and angiogenesis. MCs are also one of the primary sources of cathelicidin LL-37 (Cath LL-37), an antimicrobial peptide that has been shown to be an enabler of rosacea pathogenesis. Here, we demonstrate that MCs are key mediators of cathelicidin-initiated skin inflammation. After Cath LL-37 injection into the dermis, MC-deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (KitW-sh) mice did not develop rosacea-like features. Conversely, chymase (P
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- 2014
55. UVB Radiation Illuminates the Role of TLR3 in the Epidermis
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Borkowski, Andrew W and Gallo, Richard L
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Biomedical and Clinical Sciences ,Clinical Sciences ,Climate-Related Exposures and Conditions ,Autoimmune Disease ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Skin ,DNA Damage ,Epidermis ,Humans ,Skin Diseases ,Toll-Like Receptor 3 ,Ultraviolet Rays ,Oncology and Carcinogenesis ,Dermatology & Venereal Diseases ,Clinical sciences - Abstract
UV radiation poses a significant risk to human health. The mechanisms that help repair UV-damaged cells have recently been more clearly defined with the observation that Toll-like receptor 3 can sense self RNA released from necrotic keratinocytes following UV damage. TLR3 activation in the skin induces inflammation and increases the expression of genes involved in skin barrier repair. Activation of TLR2 in the skin by commensal microbial products prevents excessive inflammation by blocking downstream TLR3 signaling. This review highlights how UV damage-induced inflammation in the skin is propagated by host products and regulated by host inhabitants.
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- 2014
56. Hyaluronan Breakdown Contributes to Immune Defense against Group A Streptococcus *
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Schommer, Nina N, Muto, Jun, Nizet, Victor, and Gallo, Richard L
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Medical Microbiology ,Biomedical and Clinical Sciences ,Biological Sciences ,Infectious Diseases ,2.2 Factors relating to the physical environment ,Aetiology ,Infection ,Animals ,Bacterial Capsules ,Cell Line ,Humans ,Hyaluronic Acid ,Macrophages ,Mice ,Mice ,Transgenic ,Phagocytosis ,Skin Diseases ,Bacterial ,Streptococcal Infections ,Streptococcus pyogenes ,Hyaluronan ,Hyaluronidase ,Innate Immunity ,Skin ,Chemical Sciences ,Medical and Health Sciences ,Biochemistry & Molecular Biology ,Biological sciences ,Biomedical and clinical sciences ,Chemical sciences - Abstract
Group A Streptococcus (GAS) commonly infects human skin and occasionally causes severe and life-threatening invasive diseases. The hyaluronan (HA) capsule of GAS has been proposed to protect GAS from host defense by mimicking endogenous HA, a large and abundant glycosaminoglycan in the skin. However, HA is degraded during tissue injury, and the functions of short-chain HA that is generated during infection have not been studied. To examine the impact of the molecular mass of HA on GAS infection, we established infection models in vitro and in vivo in which the size of HA was defined by enzymatic digestion or custom synthesis. We discovered that conversion of high molecular mass HA to low molecular mass HA facilitated GAS phagocytosis by macrophages and limited the severity of infection in mice. In contrast, native high molecular mass HA significantly impaired internalization by macrophages and increased GAS survival in murine blood. Thus, our data demonstrate that GAS virulence can be influenced by the size of HA derived from both the bacterium and host and suggest that high molecular mass HA facilitates GAS deep tissue infections, whereas the generation of short-chain HA can be protective.
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- 2014
57. Hyaluronan digestion controls DC migration from the skin
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Muto, Jun, Morioka, Yasuhide, Yamasaki, Kenshi, Kim, Margaret, Garcia, Andrea, Carlin, Aaron F, Varki, Ajit, and Gallo, Richard L
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Biomedical and Clinical Sciences ,Immunology ,1.1 Normal biological development and functioning ,Aetiology ,Underpinning research ,2.1 Biological and endogenous factors ,Skin ,Inflammatory and immune system ,Animals ,Cell Movement ,Dendritic Cells ,Dermatitis ,Contact ,Female ,Gene Expression ,Humans ,Hyaluronic Acid ,Hyaluronoglucosaminidase ,Male ,Mice ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Toll-Like Receptor 4 ,Medical and Health Sciences ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
The breakdown and release of hyaluronan (HA) from the extracellular matrix has been hypothesized to act as an endogenous signal of injury. To test this hypothesis, we generated mice that conditionally overexpressed human hyaluronidase 1 (HYAL1). Mice expressing HYAL1 in skin either during early development or by inducible transient expression exhibited extensive HA degradation, yet displayed no evidence of spontaneous inflammation. Further, HYAL1 expression activated migration and promoted loss of DCs from the skin. We subsequently determined that induction of HYAL1 expression prior to topical antigen application resulted in a lack of an antigenic response due to the depletion of DCs from the skin. In contrast, induction of HYAL1 expression concurrent with antigen exposure accelerated allergic sensitization. Administration of HA tetrasaccharides, before or simultaneously with antigen application, recapitulated phenotypes observed in HYAL1-expressing animals, suggesting that the generation of small HA fragments, rather than the loss of large HA molecules, promotes DC migration and subsequent modification of allergic responses. Furthermore, mice lacking TLR4 did not exhibit HA-associated phenotypes, indicating that TLR4 mediates these responses. This study provides direct evidence that HA breakdown controls the capacity of the skin to present antigen. These events may influence DC function in injury or disease and have potential to be exploited therapeutically for modification of allergic responses.
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- 2014
58. Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris
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Wang, Yanhan, Kuo, Sherwin, Shu, Muya, Yu, Jinghua, Huang, Stephen, Dai, Ashley, Two, Aimee, Gallo, Richard L, and Huang, Chun-Ming
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Microbiology ,Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Human Genome ,Complementary and Integrative Health ,Nutrition ,Genetics ,Clinical Research ,Acne Vulgaris ,Animals ,Anti-Bacterial Agents ,Antibiosis ,DNA ,Bacterial ,Fermentation ,Glycerol ,Humans ,Mice ,Molecular Sequence Data ,Probiotics ,Propionibacterium acnes ,Sequence Analysis ,DNA ,Skin ,Staphylococcus epidermidis ,Succinic Acid ,Acne ,P. acnes ,Probiotic ,S. epidermidis ,Skin microbiome ,Biotechnology - Abstract
Increasing evidence demonstrates that commensal microorganisms in the human skin microbiome help fight pathogens and maintain homeostasis of the microbiome. However, it is unclear how these microorganisms maintain biological balance when one of them overgrows. The overgrowth of Propionibacterium acnes (P. acnes), a commensal skin bacterium, has been associated with the progression of acne vulgaris. Our results demonstrate that skin microorganisms can mediate fermentation of glycerol, which is naturally produced in skin, to enhance their inhibitory effects on P. acnes growth. The skin microorganisms, most of which have been identified as Staphylococcus epidermidis (S. epidermidis), in the microbiome of human fingerprints can ferment glycerol and create inhibition zones to repel a colony of overgrown P. acnes. Succinic acid, one of four short-chain fatty acids (SCFAs) detected in fermented media by nuclear magnetic resonance (NMR) analysis, effectively inhibits the growth of P. acnes in vitro and in vivo. Both intralesional injection and topical application of succinic acid to P. acnes-induced lesions markedly suppress the P. acnes-induced inflammation in mice. We demonstrate for the first time that bacterial members in the skin microbiome can undergo fermentation to rein in the overgrowth of P. acnes. The concept of bacterial interference between P. acnes and S. epidermidis via fermentation can be applied to develop probiotics against acne vulgaris and other skin diseases. In addition, it will open up an entirely new area of study for the biological function of the skin microbiome in promoting human health.
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- 2014
59. Structure and function of the human skin microbiome
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Schommer, Nina N and Gallo, Richard L
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Genetics ,Prevention ,Human Genome ,2.2 Factors relating to the physical environment ,1.1 Normal biological development and functioning ,Underpinning research ,Aetiology ,Skin ,Infection ,Bacteria ,Bacterial Physiological Phenomena ,Biodiversity ,Fungi ,Humans ,Microbiota ,Virus Physiological Phenomena ,microbiota ,microbial diversity ,skin diseases ,skin health ,Microbiology ,Medical Microbiology - Abstract
An abundant and diverse collection of bacteria, fungi, and viruses inhabits the human skin. These microorganisms vary between individuals and between different sites on the skin. The factors responsible for the unique variability of the skin microbiome are only partly understood, but results suggest that host genetic and environmental influences play a major role. Today, the steady accumulation of data describing the skin microbiome, combined with experiments designed to test the biological functions of surface microbes, has provided new insights into links between human physiology and skin microbiota. This review describes some of the current information regarding the skin microbiome and its impact on human health. Specifically, we summarize the present understanding of the function of microbe-host interactions on the skin and highlight some unique features that distinguish skin commensal organisms from pathogenic microbes.
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- 2013
60. Functions of the skin microbiota in health and disease
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Sanford, James A and Gallo, Richard L
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Clinical Research ,Skin ,Inflammatory and immune system ,Animals ,Dysbiosis ,Humans ,Microbiota ,Keratinocyte ,Staphylococcus ,Propionibacterium acnes ,Antimicrobial peptides ,Immunology - Abstract
The skin, the human body's largest organ, is home to a diverse and complex variety of innate and adaptive immune functions. Despite this potent immune system present at the cutaneous barrier, the skin encourages colonization by microorganisms. Characterization these microbial communities has enhanced our knowledge of the ecology of organisms present in normal skin; furthermore, studies have begun to bring to light the intimate relationships shared between host and resident microbes. In particular, it is apparent that just as host immunological factors and behaviors shape the composition of these communities, microbes present on the skin greatly impact the functions of human immunity. Thus, today the skin immune system should be considered a collective mixture of elements from the host and microbes acting in a mutualistic relationship. In this article we will review recent findings of the interactions of skin microbial communities with host immunity, and discuss the role that dysbiosis of these communities plays in diseases of the skin.
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- 2013
61. Activation of TLR3 in Keratinocytes Increases Expression of Genes Involved in Formation of the Epidermis, Lipid Accumulation, and Epidermal Organelles
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Borkowski, Andrew W, Park, Kyungho, Uchida, Yoshikazu, and Gallo, Richard L
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Medical Physiology ,Biomedical and Clinical Sciences ,Genetics ,Skin ,ATP-Binding Cassette Transporters ,Cells ,Cultured ,Epidermal Cells ,Epidermis ,Gene Expression ,Humans ,Keratinocytes ,Lipid Metabolism ,Organelles ,Poly I-C ,RNA ,Double-Stranded ,RNA ,Messenger ,Toll-Like Receptor 3 ,Transcriptome ,Wound Healing ,Clinical Sciences ,Oncology and Carcinogenesis ,Dermatology & Venereal Diseases ,Clinical sciences - Abstract
Injury to the skin, and the subsequent release of noncoding double-stranded RNA (dsRNA) from necrotic keratinocytes, has been identified as an endogenous activator of Toll-like receptor 3 (TLR3). As changes in keratinocyte growth and differentiation follow injury, we hypothesized that TLR3 might trigger some elements of the barrier repair program in keratinocytes. dsRNA was observed to induce TLR3-dependent increases in human keratinocyte mRNA abundance for ABCA12 (ATP-binding cassette, sub-family A, member 12), glucocerebrosidase, acid sphingomyelinase, and transglutaminase 1. Additionally, treatment with dsRNA resulted in increases in sphingomyelin and morphologic changes including increased epidermal lipid staining by Oil Red O and TLR3-dependent increases in lamellar bodies and keratohyalin granules. These observations show that dsRNA can stimulate some events in keratinocytes that are important for skin barrier repair and maintenance.
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- 2013
62. Development of atopic dermatitis-like skin disease from the chronic loss of epidermal caspase-8
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Li, Christopher, Lasse, Samuel, Lee, Pedro, Nakasaki, Manando, Chen, Shih-Wei, Yamasaki, Kenshi, Gallo, Richard L., Jamora, Colin, and Fuchs, Elaine
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- 2010
63. De Novo Synthesis of Human Dermis in vitro in the Absence of a Three-Dimensional Scaffold
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Pouyani, Tara, Ronfard, Vincent, Scott, Paul G., Dodd, Carole M., Ahmed, Aftab, Gallo, Richard L., and Parenteau, Nancy L.
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- 2009
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64. Expression of Antimicrobial Peptides in the Normal and Involved Skin of Patients with Infective Cellulitis
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Stryjewski, Martin E., Hall, Russell P., Chu, Vivian H., Kanafani, Zeina A., O'Riordan, William D., Weinstock, Michael S., Stienecker, R. Scott, Streilein, Robert, Dorschner, Robert A., Fowler, Vance G., Corey, G. Ralph, and Gallo, Richard L.
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- 2007
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65. Host-microbiome interactions in the holobiome of atopic dermatitis.
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Burger, Elise and Gallo, Richard L.
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- 2023
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66. Endogenous antimicrobial peptides and skin infections in atopic dermatitis
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Ong, Peck Y., Ohtake, Takaaki, Brandt, Corinne, Strickland, Ian, Boguniewicz, Mark, Ganz, Tomas, Gallo, Richard L., and Leung, Donald Y.M.
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Atopic dermatitis -- Physiological aspects ,Anti-infective agents -- Research ,Skin - Abstract
The skin of people with atopic dermatitis appears to produce smaller than normal amounts of proteins that have antibiotic properties. This would explain why people with atopic dermatitis have an increased risk of skin infections. Atopic dermatitis is a chronic inflammation of the skin.
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- 2002
67. Microbiome precision editing: Using PEG as a selective fermentation initiator against methicillin-resistant Staphylococcus aureus
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Kao, Ming-Shan, Huang, Stephen, Chang, Wei-Lin, Hsieh, Ming-Fa, Huang, Chun-Jen, Gallo, Richard L, and Huang, Chun-Ming
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Methicillin-Resistant Staphylococcus aureus ,Medical Biotechnology ,Polyethylene Glycols ,Industrial Biotechnology ,Mice ,Environmental Biotechnology ,Complementary and Integrative Health ,Staphylococcus epidermidis ,Genetics ,Animals ,Humans ,Skin ,Probiotics ,Microbiota ,Hydrogels ,Staphylococcal Infections ,S. aureus ,PEG ,S. epidermidis ,Precision microbiome ,Emerging Infectious Diseases ,Infectious Diseases ,Selective fermentation ,Fermentation ,Infection ,Biotechnology - Abstract
Recent creation of a Unified Microbiome Initiative (UMI) has the aim of understanding how microbes interact with each other and with us. When pathogenic Staphylococcus aureus infects the skin, the interplay between S. aureus and skin commensal bacteria occurs. Our previous data revealed that skin commensal bacteria can mediate fermentation against the growth of USA300, a community-acquired methicillin-resistant S. aureus MRSA. By using a fermentation process with solid media on a small scale, we define poly(ethylene glycol) dimethacrylate (PEG-DMA) as a selective fermentation initiator which can specifically intensify the probiotic ability of skin commensal Staphylococcus epidermidis bacteria. At least five short-chain fatty acids including acetic, butyric and propionic acids with anti-USA300 activities are produced by PEG-DMA fermentation of S. epidermidis. Furthermore, the S. epidermidis-laden PEG-DMA hydrogels effectively decolonized USA300 in skin wounds in mice. The PEG-DMA and its derivatives may become novel biomaterials to specifically tailor the human skin microbiome against invading pathogens.
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- 2017
68. Staphylococcus epidermidis activates keratinocyte cytokine expression and promotes skin inflammation through the production of phenol-soluble modulins.
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Williams, Michael R., Bagood, Michelle D., Enroth, Timothy J., Bunch, Zoie L., Jiang, Nina, Liu, Edward, Almoughrabie, Samia, Khalil, Shadi, Li, Fengwu, Brinton, Samantha, Cech, Nadja B., Horswill, Alexander R., and Gallo, Richard L.
- Abstract
Staphylococcus epidermidis is a common microbe on human skin and has beneficial functions in the skin microbiome. However, under conditions of allergic inflammation, the abundance of S. epidermidis increases, establishing potential danger to the epidermis. To understand how this commensal may injure the host, we investigate phenol-soluble modulin (PSM) peptides produced by S. epidermidis that are similar to peptides produced by Staphylococcus aureus. Synthetic S. epidermidis PSMs induce expression of host defense genes and are cytotoxic to human keratinocytes. Deletion mutants of S. epidermidis lacking these gene products support these observations and further show that PSMs require the action of the EcpA bacterial protease to induce inflammation when applied on mouse skin with an intact stratum corneum. The expression of PSMδ from S. epidermidis is also found to correlate with disease severity in patients with atopic dermatitis. These observations show how S. epidermidis PSMs can promote skin inflammation. [Display omitted] • S. epidermidis phenol-soluble modulins promote cytokine expression by keratinocytes • S. epidermidis PSMs with EcpA induce murine Type 17 skin inflammation • S. epidermidis PSM levels are elevated in human atopic dermatitis Williams et al. show that the skin microbe Staphylococcus epidermidis can produce phenol-soluble modulins (PSMs) that will induce skin inflammation. These PSMs combine with cysteine proteases to promote skin disease. [ABSTRACT FROM AUTHOR]
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- 2023
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69. Mast Cell Cathelicidin Antimicrobial Peptide Prevents Invasive Group A Streptococcus Infection of the Skin1
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Di Nardo, Anna, Yamasaki, Kenshi, Dorschner, Robert A., Lai, Yuping, and Gallo, Richard L.
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Neutrophils ,Streptococcus pyogenes ,Colony Count, Microbial ,Bacteremia ,Skin Diseases, Bacterial ,Article ,Mice, Mutant Strains ,Mice ,Neutrophil Infiltration ,Cathelicidins ,Streptococcal Infections ,Animals ,Mast Cells ,Antimicrobial Cationic Peptides ,Skin - Abstract
Mast cells (MC) express cathelicidin antimicrobial peptides that act as broad-spectrum antibiotics and influence the immune defense of multiple epithelial surfaces. We hypothesized that MC help protect against skin infection through the expression of cathelicidin. The susceptibility of MC-deficient mice (Kit Wsh(-/-)) to invasive group A streptococcus (GAS) was compared with control mice. Following s.c. injection of GAS, MC-deficient mice had 30% larger skin lesions, 80% more lesional bacteria, and 30% more spleens positive for bacteria. In contrast to results obtained when GAS was injected into skin, no significant differences were noted between MC-deficient mice and control mice after GAS was applied topically, indicating that MC activity is most important after barrier penetration. To determine whether these differences were due to MC expression of cathelicidin, MC-deficient mice were reconstituted with MC derived from either wild-type or cathelicidin-deficient (Camp(-/-)) mice and challenged with GAS. Forty-eight hours after bacterial injection, mice that did not receive MC had an average lesion size of 200 mm(2), mice reconstituted with wild-type MC showed lesions comparable to control mice (25 mm(2)), while mice reconstituted with Camp(-/-) MC showed an average lesion size of 120 mm(2). Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) analysis of cathelicidin peptide purified from mast cells defined this as a unique 28-aa peptide. Combined, these results show that MC confer defense against Gram-positive bacterial infection in the skin, a function mediated in part by the expression of a unique cathelicidin peptide.
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- 2008
70. A Precision Microbiome Approach Using Sucrose for Selective Augmentation of Staphylococcus epidermidis Fermentation against Propionibacterium acnes.
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Yanhan Wang, Ming-Shan Kao, Jinghua Yu, Stephen Huang, Shinta Marito, Gallo, Richard L., and Chun-Ming Huang
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HUMAN microbiota ,CUTIBACTERIUM acnes ,STAPHYLOCOCCUS epidermidis ,GLYCEROLIPIDS ,NUCLEAR magnetic resonance - Abstract
Acne dysbiosis happens when there is a microbial imbalance of the over-growth of Propionibacterium acnes (P. acnes) in the acne microbiome. In our previous study, we demonstrated that Staphylococcus epidermidis (S. epidermidis, a probiotic skin bacterium) can exploit glycerol fermentation to produce short-chain fatty acids (SCFAs) which have antimicrobial activities to suppress the growth of P. acnes. Unlike glycerol, sucrose is chosen here as a selective fermentation initiator (SFI) that can specifically intensify the fermentation activity of S. epidermidis, but not P. acnes. A co-culture of P. acnes and fermenting S. epidermidis in the presence of sucrose significantly led to a reduction in the growth of P. acnes. The reduction was abolished when P. acnes was co-cultured with non-fermenting S. epidermidis. Results from nuclear magnetic resonance (NMR) analysis revealed four SCFAs (acetic acid, butyric acid, lactic acid, and succinic acid) were detectable in the media of S. epidermidis sucrose fermentation. To validate the interference of S. epidermidis sucrose fermentation with P. acnes, mouse ears were injected with both P. acnes and S. epidermidis plus sucrose or phosphate buffered saline (PBS). The level of macrophage-inflammatory protein-2 (MIP-2) and the number of P. acnes in ears injected with two bacteria plus sucrose were considerably lower than those in ears injected with two bacteria plus PBS. Our results demonstrate a precision microbiome approach by using sucrose as a SFI for S. epidermidis, holding future potential as a novel modality to equilibrate dysbiotic acne. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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71. Hyaluronic Acid Oligosaccharides Suppress TLR3-Dependent Cytokine Expression in a TLR4-Dependent Manner.
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Kim, Margaret Y., Muto, Jun, and Gallo, Richard L.
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HYALURONIC acid ,OLIGOSACCHARIDES ,TOLL-like receptors ,CYTOKINES ,INFLAMMATION ,SKIN wound treatment ,IMMUNOREGULATION - Abstract
The release of endogenous molecules from the skin after injury has been proposed to influence inflammation. Recent studies have found that pro-inflammatory signals can be generated by damaged endogenous self-RNA, and this event is detected by TLR3. Conversely, release of endogenous fragments of hyaluronic acid (HA) after injury has been proposed to inhibit LPS induced inflammation driven by TLR4. In this study we investigated if HA oligomers could also influence inflammation mediated by TLR3. A tetramer form of HA (oligo-HA) was added to MH-S cells (mouse alveolar macrophage cell line) that were then activated by poly(I:C). ELISA analysis of culture supernatants showed that the presence of oligo-HA suppressed the poly(I:C) induced release of IL-6 and TNFα. IL-6 mRNA expression was also suppressed as measured by quantitative RT-PCR. To determine the mechanism of action for oligo-HA to inhibit poly(I:C), macrophages derived from wild-type (WT), Tlr2−/− or Tlr4−/− mice were treated with oligo-HA and poly(I:C). Similar to WT cells, Tlr2−/− macrophages were inhibited by oligo-HA and retained suppression of cytokine release. In contrast, Tlr4−/− macrophages lost the capacity to be suppressed by oligo-HA. An increase in Traf1 (TLR negative regulator) mRNA was observed after oligo-HA treatment of WT but not in Tlr4−/− macrophages, and oligo-HA did not suppress cytokine responsiveness in Traf1−/− macrophages. These results show that oligo-HA acts through TLR4 and TRAF1 to inhibit TLR3-dependent inflammation. This observation illustrates the complex immunomodulatory action of endogenous products released after injury. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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72. The Response of Human Skin Commensal Bacteria as a Reflection of UV Radiation: UV-B Decreases Porphyrin Production.
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Yanhan Wang, Wenhong Zhu, Muya Shu, Yong Jiang, Gallo, Richard L., Yu-Tsueng Liu, and Chun-Ming Huang
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CUTIBACTERIUM acnes ,ULTRAVIOLET radiation ,PORPHYRINS ,SKIN ,LABORATORY mice ,CANCER research - Abstract
Recent global radiation fears reflect the urgent need for a new modality that can simply determine if people are in a radiation risk of developing cancer and other illnesses. Ultraviolet (UV) radiation has been thought to be the major risk factor for most skin cancers. Although various biomarkers derived from the responses of human cells have been revealed, detection of these biomarkers is cumbersome, probably requires taking live human tissues, and varies significantly depending on human immune status. Here we hypothesize that the reaction of Propionibacterium acnes (P. acnes), a human resident skin commensal, to UV radiation can serve as early surrogate markers for radiation risk because the bacteria are immediately responsive to radiation. In addition, the bacteria can be readily accessible and exposed to the same field of radiation as human body. To test our hypothesis, P. acnes was exposed to UV-B radiation. The production of porphyrins in P. acnes was significantly reduced with increasing doses of UV-B. The porphyrin reduction can be detected in both P. acnes and human skin bacterial isolates. Exposure of UV-B to P. acnes- inoculated mice led to a significant decrease in porphyrin production in a single colony of P. acnes and simultaneously induced the formation of cyclobutane pyrimidine dimers (CPD) in the epidermal layers of mouse skin. Mass spectrometric analysis via a linear trap quadrupole (LTQ)-Orbitrap XL showed that five peptides including an internal peptide (THLPTGIVVSCQNER) of a peptide chain release factor 2 (RF2) were oxidized by UV-B. Seven peptides including three internal peptides of 60 kDa chaperonin 1 were de-oxidized by UV-B. When compared to UV-B, gamma radiation also decreased the porphyrin production of P. acnes in a dose-dependent manner, but induced a different signature of protein oxidation/de-oxidation. We highlight that uncovering response of skin microbiome to radiation will facilitate the development of pre-symptomatic diagnosis of radiation risk in a battlefield exposure, nuclear accidents, terrorist attacks, or cancer imaging/therapy. [ABSTRACT FROM AUTHOR]
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- 2012
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73. Recognizing that the microbiome is part of the human immune system will advance treatment of both cancer and infections.
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Gallo, Richard L., Hultsch, Thomas, and Farnaes, Lauge
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- 2016
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74. The vitamin D pathway: a new target for control of the skin’s immune response?
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Schauber, Jürgen and Gallo, Richard L.
- Subjects
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DERMATOMYCOSES , *PATHOGENIC microorganisms , *PEPTIDE antibiotics , *NEUROPEPTIDES , *CYTOKINES - Abstract
The surface of our skin is constantly challenged by a wide variety of microbial pathogens, still cutaneous infections are relatively rare. Within cutaneous innate immunity the production of antimicrobial peptides (AMPs) is a primary system for protection against infection. Many AMPs can be found on the skin, and these include molecules that were discovered for their antimicrobial properties, and other peptides and proteins first known for activity as chemokines, enzymes, enzyme inhibitors and neuropeptides. Cathelicidins were among the first familiesf of AMPs discovered on the skin. They are now known to have two distinct functions; they have direct antimicrobial activity and will initiate a host cellular response resulting in cytokine release, inflammation and angiogenesis. Dysfunction of cathelicidin is relevant in the pathogenesis of several cutaneous diseases including atopic dermatitis where cathelicidin induction is suppressed, rosacea, where cathelicidin peptides are abnormally processed to forms that induce cutaneous inflammation and a vascular response, and psoriasis, where a cathelicidin peptide can convert self-DNA to a potent stimulus of an autoinflammatory cascade. Recent work has unexpectedly identified vitamin D3 as a major factor involved in the regulation of cathelicidin expression. Therapies targeting the vitamin D3 pathway and thereby cathelicidin may provide new treatment modalities in the management of infectious and inflammatory skin diseases. [ABSTRACT FROM AUTHOR]
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- 2008
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75. Antimicrobial peptides and the skin immune defense system.
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Schauber, Jürgen and Gallo, Richard L.
- Subjects
SKIN inflammation ,NEOVASCULARIZATION ,PROTEINS ,PEPTIDES - Abstract
Our skin is constantly challenged by microbes but is rarely infected. Cutaneous production of antimicrobial peptides (AMPs) is a primary system for protection, and expression of some AMPs further increases in response to microbial invasion. Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways: (1) direct antimicrobial activity and (2) initiation of a host response resulting in cytokine release, inflammation, angiogenesis, and reepithelialization. Cathelicidin dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including atopic dermatitis, in which cathelicidin is suppressed; rosacea, in which cathelicidin peptides are abnormally processed to forms that induce inflammation; and psoriasis, in which cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent work identified vitamin D3 as a major factor involved in the regulation of cathelicidin. Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
76. Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli.
- Author
-
Schauber, Jürgen, Dorschner, Robert A., Yamasaki, Kenshi, Brouha, Brook, and Gallo, Richard L.
- Subjects
ANTI-infective agents ,MUCOUS membranes ,GENETIC regulation ,HUMAN beings ,SKIN ,EPITHELIAL cells - Abstract
Immune defence against microbes depends in part on the production of antimicrobial peptides, a process that occurs in a variety of cell types but is incompletely understood. In this study, the mechanisms responsible for the induction of cathelicidin and β-defensin antimicrobial peptides were found to be independent and specific to the cell type and stimulus. Vitamin D
3 induced cathelicidin expression in keratinocytes and monocytes but not in colonic epithelial cells. Conversely, butyrate induced cathelicidin in colonic epithelia but not in keratinocytes or monocytes. Distinct factors induced β-defensin expression. In all cell types, vitamin D3 activated the cathelicidin promoter and was dependent on a functional vitamin D responsive element. However, in colonic epithelia butyrate induced cathelicidin expression without increasing promoter activity and vitamin D3 activated the cathelicidin promoter without a subsequent increase in transcript accumulation. Induction of cathelicidin transcript correlated with increased processed mature peptide and enhanced antimicrobial activity against Staphylococcus aureus. However, induction of β-defensin-2 expression did not alter the innate antimicrobial capacity of cells in culture. These data suggest that antimicrobial peptide expression is regulated in a tissue-specific manner at transcriptional, post-transcriptional and post-translational levels. Furthermore, these data show for the first time that innate antimicrobial activity can be triggered independently of the release of other pro-inflammatory molecules, and suggest strategies for augmenting innate immune defence without increasing inflammation. [ABSTRACT FROM AUTHOR]- Published
- 2006
- Full Text
- View/download PDF
77. Antimicrobial Peptides: An Emerging Concept in Cutaneous Biology.
- Author
-
Gallo, Richard L. and Huttner, Kenneth M.
- Subjects
- *
ANTIMICROBIAL peptides , *SKIN , *NATURAL immunity - Abstract
Antimicrobial peptides are part of the host defense systems of plants, insects, fish, amphibia, birds, and mammals. These small proteins were previously thought of as an evolutionarily ancient system of immune protection with little relevance to the normal function of human skin. Recent developments have found that mammalian skin expresses these gene-encoded peptide antibiotics during inflammatory events such as wound repair, contact dermatitis, and psoriasis. The presence of these peptides in the skin forms a barrier for innate host protection against microbial pathogenesis. Furthermore, antimicrobial peptides also act on animal cells by stimulating them to change behaviors such as syndecan expression, chemotaxis, and chloride secretion. The combination of effects on host cells with antimicrobial action in a single molecule represents an efficient defense and response system against injury. Understanding the action of antimicrobial peptides in skin may yield further insight into the mechanism of innate cutaneous disease control and provide new approaches to therapy of wounds and inflammatory dermatitis. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
78. The birth of innate immunity.
- Author
-
Gallo, Richard L.
- Subjects
- *
IMMUNOLOGY , *IMMUNE system , *BONE marrow , *LEUCOCYTES , *EPITHELIAL cells - Abstract
Modern immunology has seen an apparent revolution with the recognition that human immune defense is not only the responsibility of bone marrow-derived leucocytes, but also dependent on a coordinated network of many cell types including epithelial cells, fibroblasts and neural elements. This classic paper by Alexander Fleming and V.D. Allison (British J of Exp Path, 111, 1922, 252) was largely forgotten for 75 years and describes the discovery that epithelia produce a protein with direct antimicrobial activity. Thus, this paper represents the birth of the field now referred to as innate immunity and first describes an antimicrobial protein ( AMP). [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
79. Sounding the Alarm: Multiple Functions of Host Defense Peptides.
- Author
-
Gallo, Richard L.
- Subjects
- *
PEPTIDES , *INFECTION , *SKIN , *IMMUNE response , *ANTIBIOTICS , *KERATINOCYTES , *CELL lines - Abstract
The capacity of the skin and other organs to resist infection depends on the innate production of molecules known as antimicrobial peptides. Emerging evidence suggests that some of these peptides are important to immune defense by acting not only as natural antibiotics but also as cell-signaling molecules. In this issue Carretero et al. (2007) expand on these findings by demonstrating that expression of human cathelicidin alters multiple signaling pathways in a keratinocyte cell line and enhances wound re-epithelialization in ob/ob mice.Journal of Investigative Dermatology (2008) 128, 5–6. doi:10.1038/sj.jid.5701073 [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
80. Antimicrobial peptides and the skin immune defense system.
- Author
-
Schauber, Jürgen and Gallo, Richard L.
- Subjects
ANTIMICROBIAL peptides ,IMMUNE system ,IMMUNOLOGY of inflammation ,DISEASE management ,SKIN disease genetics ,ATOPIC dermatitis ,ROSACEA ,PSORIASIS ,GENETICS - Abstract
Our skin is constantly challenged by microbes but is rarely infected. Cutaneous production of antimicrobial peptides (AMPs) is a primary system for protection, and expression of some AMPs further increases in response to microbial invasion. Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways: (1) direct antimicrobial activity and (2) initiation of a host response resulting in cytokine release, inflammation, angiogenesis, and reepithelialization. Cathelicidin dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including atopic dermatitis, in which cathelicidin is suppressed; rosacea, in which cathelicidin peptides are abnormally processed to forms that induce inflammation; and psoriasis, in which cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent work identified vitamin D3 as a major factor involved in the regulation of cathelicidin. Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
81. Antimicrobial and Protease Inhibitory Functions of the Human Cathelicidin (hCAP18/LL-37) Prosequence.
- Author
-
Zaiou, Mohamed, Nizet, Victor, and Gallo, Richard L.
- Subjects
- *
PEPTIDE antibiotics , *SKIN , *PROTEOLYTIC enzymes - Abstract
Cathelicidins are a class of small cationic peptide antibiotics that are expressed in skin and in other epithelial cells and are an active component of mammalian innate immunity. Human cathelicidin (hCAP18/LL-37) consists of a conserved prosequence called the cathelin-like domain and a C-terminal peptide named LL-37. To date, our understanding of the cathelin-like domain was very limited. To bring insight into the function of this evolutionarily conserved prosequence, we produced recombinant human cathelin-like protein and full-length hCAP18/LL-37 in Escherichia coli . As the cathelin-like protein shares homology with the cystatin family of cysteine protease inhibitors, we first analyzed the effect of the cathelin-like recombinant protein on the cysteine protease cathepsin L. We found that the cathelin-like protein inhibited protease activity. Next, we tested the cathelin-like protein for antimicrobial activity using solid phase radial diffusion and liquid phase killing assays. The cathelin-like prosequence, but not full-length hCAP18/LL-37, killed human pathogens including E. coli and methicillin-resistant Staphylococcus aureus at concentrations ranging from 16 to 32 μM. Together these findings suggest that after proteolytic cleavage the cathelin-like domain can contribute to innate host defense through inhibition of bacterial growth and limitation of cysteine-proteinase-mediated tissue damage. As these dual functions are complementary to the LL-37 peptide released from the C-terminus of full-length hCAP18/LL-37, human cathelicidin represents an elegant multifunctional effector molecule for innate immune defense of the skin. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
82. Skin surface lipidomics revealed the correlation between lipidomic profile and grade in adolescent acne.
- Author
-
Zhou, Mingyue, Yang, Manli, Zheng, Yumei, Dong, Kun, Song, Liya, He, Congfen, Liu, Wei, Wang, Yiyu, and Jia, Yan
- Subjects
ACNE ,ADOLESCENT development ,ADOLESCENCE ,SKIN ,FATTY acids - Abstract
Background: Acne is a multifactorial skin disorder frequently observed during adolescence with different grades of severity. The crucial factors of acne are the increase of lipids secretion and the change of composition on the skin surface lipid (SSL). However, there are no studies on the changes of lipid composition and content between different grades of adolescent acne in lesional skin and nonlesionsal skin. Aims: This study was to investigate correlation in the composition of SSL and different grades in order to understand the tendency of SSL alterations in this disease for successful acne management and prevention. Methods: A powerful analytical technique, UPLC‐QTOF‐MS, and multivariate data analysis were used to investigate SSL variations of lipid main classes, subclasses, and species. Results: The results indicated that sphinganine, triradylglycerols (TG), and phytosphingosine were important in adolescent acne development. The average fatty acids (FAs) chain length in patients with acne showed significantly shortened trend from mild to moderate adolescent acne. Additionally, the relative average content of TG, diglyceride (DG), FA, ceramides (Cers), and the level of unsaturated FAs significantly increased from mild to moderate adolescent acne. Interestingly, our results demonstrated that the phytosphingosine and sphinganine showed an increasing trend in mild acne groups, but decreasing trend in lesional skin of moderate group. Conclusions: Lipidomics analysis suggested that the variation of TG, phytosphingosine, and sphinganine was closely related to the occurrence severity of acne in adolescent. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
83. Activation of Parathyroid Hormone 2 Receptor Induces Decorin Expression and Promotes Wound Repair
- Author
-
Biswa Choudhury, Robert A. Dorschner, Ling-juan Zhang, Richard L. Gallo, Emi Sato, and Christopher A. Adase
- Subjects
Keratinocytes ,0301 basic medicine ,Decorin ,Vesicular Transport Proteins ,Parathyroid hormone ,Inbred C57BL ,Biochemistry ,Extracellular matrix ,Mice ,Receptor ,Cells, Cultured ,Skin ,Cultured ,biology ,Chemistry ,RNA-Binding Proteins ,Nuclear Proteins ,Cell Differentiation ,Extracellular Matrix ,Cell biology ,Parathyroid Hormone ,Parathyroid hormone 2 receptor ,Female ,RNA Splicing Factors ,Type 2 ,Signal Transduction ,medicine.medical_specialty ,Cells ,1.1 Normal biological development and functioning ,Immunoblotting ,Clinical Sciences ,Oncology and Carcinogenesis ,Dermatology ,Real-Time Polymerase Chain Reaction ,Article ,Receptor, Parathyroid Hormone, Type 2 ,03 medical and health sciences ,Internal medicine ,medicine ,Extracellular ,Animals ,Humans ,Molecular Biology ,Receptor, Parathyroid Hormone, Type 1 ,Wound Healing ,5.2 Cellular and gene therapies ,Animal ,Dermatology & Venereal Diseases ,Cell Biology ,Mice, Inbred C57BL ,carbohydrates (lipids) ,Fibronectin ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Proteoglycan ,Disease Models ,biology.protein ,RNA ,Wounds and Injuries - Abstract
In this study, we report that TIP39, a parathyroid hormone ligand family member that was recently identified to be expressed in the skin, can induce decorin expression and enhance wound repair. Topical treatment of mice with TIP39 accelerated wound repair, whereas TIP39-deficient mice had delayed repair that was associated with formation of abnormal collagen bundles. To study the potential mechanism responsible for the action of TIP39 in the dermis, fibroblasts were cultured in three-dimensional collagen gels, a process that results in enhanced decorin expression unless activated to differentiate to adipocytes, whereupon these cells reduce expression of several proteoglycans, including decorin. Small interfering RNA-mediated silencing of parathyroid hormone 2 receptor (PTH2R), the receptor for TIP39, suppressed the expression of extracellular matrix-related genes, including decorin, collagens, fibronectin, and matrix metalloproteases. Skin wounds in TIP39 –/– mice had decreased decorin expression, and addition of TIP39 to cultured fibroblasts induced decorin and increased phosphorylation and nuclear translocation of CREB. Fibroblasts differentiated to adipocytes and treated with TIP39 also showed increased decorin and production of chondroitin sulfate. Furthermore, the skin of PTH2R –/– mice showed abnormal extracellular matrix structure, decreased decorin expression, and skin hardness. Thus, the TIP39-PTH2R system appears to be a previously unrecognized mechanism for regulation of extracellular matrix formation and wound repair.
- Published
- 2017
84. Granulysin-Derived Peptides Demonstrate Antimicrobial and Anti-Inflammatory Effects Against Propionibacterium acnes.
- Author
-
McInturff, Jamie E., Wang, Shyh-Jeun, Machleidt, Thomas, Lin, T . Richard, Oren, Ami, Hertz, Cheryl J., Krutzik, Stephan R., Hart, Scott, Zeh, Karin, Anderson, Daniel H., Gallo, Richard L., Modlin, Robert L., and Kim, Jenny
- Subjects
- *
CUTIBACTERIUM acnes , *ANTIBIOTICS , *ANTI-infective agents , *PEPTIDES , *TRYPTOPHAN , *PROTEOLYTIC enzymes - Abstract
Propionibacterium acnes is a key therapeutic target in acne, yet this bacterium has become resistant to standard antibiotic agents. We investigated whether the human antimicrobial protein granulysin is a potential candidate for the treatment of acne. Granulysin and synthetic granulysin-derived peptides possessing a helix–loop–helix motif killed P. acnes in vitro. Modification of a helix–loop–helix peptide, 31–50, by substitution of a tryptophan for the valine at amino acid 44 (peptide 31–50v44w) to increase its interaction with bacterial surfaces also increased its antimicrobial activity. Moreover, when synthesized with d- rather than l-type amino acids, this peptide ( d-31–50v44w) became less susceptible to degradation by proteases and more effective in killing P. acnes. Granulysin peptides were bactericidal, demonstrating an advantage over standard bacteriostatic antibiotics in their control of P. acnes. Moreover, peptide d-31–50v44w killed P. acnes in isolated human microcomedone preparations. Importantly, peptides 31–50, 31–50v44w, and d-31–50v44w also have potential anti-inflammatory effects, as demonstrated by suppression of P. acnes-stimulated cytokine release. Taken together, these data suggest that granulysin peptides may be useful as topical therapeutic agents, providing alternatives to current acne therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
85. Cutaneous Injury Induces the Release of Cathelicidin Anti-Microbial Peptides Active Against Group A Streptococcus.
- Author
-
Dorschner, Robert A., Pestonjamasp, Vasumati K., Tamakuwala, Seema, Ohtake, Takaaki, Rudisill, Jennifer, Nizet, Victor, Agerberth, Birgitta, Gudmundsson, Gudmunder H., and Gallo, Richard L.
- Subjects
- *
SKIN diseases , *STREPTOCOCCAL diseases - Abstract
Cathelicidins are a family of peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. The human and mouse cathelicidins (LL-37 and CRAMP, respectively) are expressed at select epithelial interfaces where they have been proposed to kill a number of gram-negative and gram-positive bacteria. To determine if these peptides play a part in the protection of skin against wound infections, the anti-microbial activity of LL-37 and CRAMP was determined against the common wound pathogen group A Streptococcus, and their expression was examined after cutaneous injury. We observed a large increase in the expression of cathelicidins in human and murine skin after sterile incision, or in mouse following infection by group A Streptococcus. The appearance of cathelicidins in skin was due to both synthesis within epidermal keratinocytes and deposition from granulocyctes that migrate to the site of injury. Synthesis and deposition in the wound was accompanied by processing from the inactive prostorage form to the mature C-terminal peptide. Analysis of anti-microbial activity of this C-terminal peptide against group A Streptococcus revealed that both LL-37 and CRAMP potently inhibited bacterial growth. Action against group A Streptococcus occurred in conditions that typically abolish the activity of anti-microbial peptides against other organisms. Thus, cathelicidins are well suited to provide defense against infections due to group A Streptococcus, and represent an important element of cutaneous innate immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
86. Anti-Microbial Activity and Cell Binding are Controled by Sequence Determinants in the Anti-Microbial Peptide PR-39.
- Author
-
Chan, Yvonne R., Zanetti, Margherita, Gennaro, Renato, and Gallo, Richard L.
- Subjects
- *
PROLINE , *SKIN , *ARGININE - Abstract
Summary PR-39 is a member of the proline-rich group of cathelicidin peptides, a class of anti-microbial peptides found in skin and in leukocytes. In addition to their innate defense function, these proline-rich peptides influence a number of mammalian cell processes, including inflammation, development, differentiation, and metastatic transformation. To characterize the mechanism further, through which proline-rich cathelicidin peptides may exert their numerous effects, we altered various conserved peptide sequence motifs using a biologically active fragment of PR-39 [PR-39(15)] as the template: We altered the N-terminal charge of its SH3 binding motif, substituted tryptophan for a conserved intervening leucine, and modified a proline–arginine stretch (residues 10–13). These peptide variants were tested for binding known targets of PR-39 and for biologic activity in mammalian and bacterial systems. We found that the N-terminal arginines are crucial for protein binding and that modification in this domain results in loss of affinity and specificity in binding to generalized and SH3-containing targets. The N-terminal charged residues are also required for NIH 3T3 syndecan induction and anti-microbial activity. In addition, modification of more C-terminal residues eliminates anti-bacterial activity while having less of an effect on peptide interactions in mammalian cell assays. This study shows that the presence of a charged N-terminus is important for peptide activity in both mammalian and bacterial systems whereas the C-terminal alterations of PR-39(15) more definitively affect anti-bacterial activity. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
87. M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil extracellular entrapment
- Author
-
Maren von Köckritz-Blickwede, Victor Nizet, Anjuli M. Timmer, Richard L. Gallo, Suzan H.M. Rooijakkers, Laura E. Crotty Alexander, and Heather C. Maisey
- Subjects
Neutrophils ,Fimbria ,medicine.disease_cause ,Neutrophil extracellular traps ,Virulence factor ,Pilus ,Mice ,Drug Discovery ,Genetics(clinical) ,Genetics (clinical) ,Skin ,Medicine(all) ,0303 health sciences ,Virulence ,Streptococcus ,Group A Streptococcus ,3. Good health ,medicine.anatomical_structure ,Molecular Medicine ,Original Article ,Female ,Streptococcus pyogenes ,Biology ,Granulocyte ,Microbiology ,03 medical and health sciences ,Phagocytosis ,Streptococcal Infections ,Internal Medicine ,Cell Adhesion ,medicine ,Animals ,Humans ,030304 developmental biology ,IL-8 ,030306 microbiology ,Macrophages ,Interleukin-8 ,Human Genetics ,Epithelial Cells ,Biomedicine ,Mutagenesis ,Fimbriae, Bacterial ,Immunology - Abstract
Group A Streptococcus is a leading human pathogen associated with a diverse array of mucosal and systemic infections. Cell wall anchored pili were recently described in several species of pathogenic streptococci, and in the case of GAS, these surface appendages were demonstrated to facilitate epithelial cell adherence. Here we use targeted mutagenesis to evaluate the contribution of pilus expression to virulence of the globally disseminated M1T1 GAS clone, the leading agent of both GAS pharyngitis and severe invasive infections. We confirm that pilus expression promotes GAS adherence to pharyngeal cells, keratinocytes, and skin. However, in contrast to findings reported for group B streptococcal and pneumococcal pili, we observe that pilus expression reduces GAS virulence in murine models of necrotizing fasciitis, pneumonia and sepsis, while decreasing GAS survival in human blood. Further analysis indicated the systemic virulence attenuation associated with pilus expression was not related to differences in phagocytic uptake, complement deposition or cathelicidin antimicrobial peptide sensitivity. Rather, GAS pili were found to induce neutrophil IL-8 production, promote neutrophil transcytosis of endothelial cells, and increase neutrophil release of DNA-based extracellular traps, ultimately promoting GAS entrapment and killing within these structures.
- Published
- 2009
88. Discovery of a novel parathyroid hormone family member in skin that regulates keratinocyte differentiation.
- Author
-
Sato, Emi, Muto, Jun, Zhang, Ling-juan, Adase, Christopher, Sanford, James A., Nakatsuji, Teruaki, and Gallo, Richard L.
- Subjects
- *
PARATHYROID glands , *SKIN , *DERMATOLOGY , *INFLAMMASOMES ,KERATINOCYTE differentiation - Published
- 2016
- Full Text
- View/download PDF
89. Patent Application Titled 'Prevention Of Rosacea Inflammation' Published Online (USPTO 20230181518)
- Subjects
Amino acids -- Intellectual property ,Aprotinin ,Skin ,Physical fitness ,Health - Abstract
2023 JUL 8 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a [...]
- Published
- 2023
90. Researchers Submit Patent Application, 'Antimicrobial Therapy', for Approval (USPTO 20240058395)
- Subjects
Bacteria ,Methicillin -- Intellectual property ,Skin ,Business ,Health - Abstract
2024 MAR 15 (NewsRx) -- By a News Reporter-Staff News Editor at Medical Patent Business Week -- From Washington, D.C., NewsRx journalists report that a patent application by the inventors [...]
- Published
- 2024
91. Patent Application Titled 'Prevention Of Rosacea Inflammation' Published Online (USPTO 20200215023)
- Subjects
Pemirolast ,Physical fitness ,Aprotinin ,Amino acids -- Intellectual property ,Skin ,Health - Abstract
2020 AUG 1 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a [...]
- Published
- 2020
92. Patent Application Titled 'Prevention Of Rosacea Inflammation' Published Online (USPTO 20180221331)
- Subjects
Physical fitness ,Aliphatic acids -- Intellectual property ,Patents ,Amino acids -- Intellectual property ,Skin ,Patent/copyright issue ,Health - Abstract
2018 SEP 1 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a [...]
- Published
- 2018
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