Search

Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is treated with immunosuppressants. However, long‐term use of immunosuppressants may cause toxicity and severe side‐effects. To confirm the long‐term efficacy and safety of clonal mesenchymal stem cell therapy, we performed investigator‐initiated clinical trials and long‐term observation in five adult patients with moderate to severe atopic dermatitis that was refractory to conventional treatments. The clinical response assessment values such as Eczema Area and Severity Index (EASI) improved significantly at 16 weeks, and 80% (4/5) of the patients achieved EASI‐50 after one or two treatment cycles. Patients were observed for long‐term efficacy and safety for an average of 38 weeks (range, 16–86) and showed no serious side‐effects. Among the cytokines tested, CCL‐17, interleukin (IL)‐13, and IL‐22 significantly decreased at the end‐point of the five participants, two patients who maintained good clinical response over 84 weeks showed increased IL‐17 cytokine levels in the blood. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease. A hallmark of AD is dry itchy skin that results from defects in the epidermal barrier function. Aloe vera is used widely to promote general health and is administered topically to treat skin conditions such as eczema, burns and wounds. However, effects of A vera on AD were not fully elucidated. In this study, we investigated the oral administration of processed A vera gel (PAG) containing low molecular weight Aloe polysaccharides to treat ovalbumin (OVA)‐induced AD in mice. Oral administration of PAG suppressed total and OVA‐specific IgE production in sera and decreased the epidermal thickness of skin. Numbers of Ki‐67‐positive cells were reduced by PAG treatment. Expression levels of tight junction genes, including those that encode ZO‐1, Claudin‐1 and Claudin‐8, were decreased in AD skin lesions, whereas oral administration of PAG partially restored the expression levels of tight junction genes. In addition, IL‐4 and IL‐17A mRNA transcript levels were reduced in skin lesions after PAG treatment. Taken together, our findings suggest that oral administration of PAG ameliorated AD, normalized tight junction gene expression and suppressed inflammatory cytokines in AD skin. [ABSTRACT FROM AUTHOR]

The article discusses a study focusing on the use of bone marrow-derived mesenchymal stem cells (MSCs) to prevent alopecia areata development by inhibiting natural killer G2D (NKG2D) cell's expression. Topics discussed include the immunomodulatory and anti-inflammatory effects of MSCs on immune cells, the observance of hair loss in the mice under study, and the infiltration of the dermis by inflammatory cells, as revealed in a histological analysis.

Generation of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) induces the proliferation and migration of adipose-derived stem cells (ASCs). However, the functional role of mitochondrial ROS (mtROS) generation in ASCs is unknown. Therefore, we have investigated whether hypoxia induces the differentiation of ASCs via ROS generation. We also have tried to identify the cellular mechanisms of ROS generation underlying adipocyte differentiation. Hypoxia (2%) and ROS generators, such as antimycin and rotenone, induced adipocyte differentiation, which was attenuated by an ROS scavenger. Although Nox4 generates ROS and regulates proliferation of ASCs, Nox4 inhibition or Nox4 silencing did not inhibit adipocyte differentiation; indeed fluorescence intensity of mito-SOX increased in hypoxia, and treatment with mito-CP, a mtROS scavenger, significantly reduced hypoxia-induced adipocyte differentiation. Phosphorylation of Akt and mTOR was induced by hypoxia, while inhibition of these molecules prevented adipocyte differentiation. Thus hypoxia induces adipocyte differentiation by mtROS generation, and the PI3K/Akt/mTOR pathway is involved. [ABSTRACT FROM AUTHOR]

Abstract: The 12/15-lipoxygenase (12/15-LOX) pathways of arachidonate metabolism have been implicated in the pathogenesis of psoriasis. Since UV photo-therapy is a commonly used technique for inhibiting cell proliferation and inflammation in skin diseases, we hypothesized that UV-irradiation may affect 12/15-LOX expression which might regulate cell proliferation. In this study, we showed that UV-irradiation suppressed 12-LOX expression, whereas up-regulated 15-LOX expression. Treatment with the 15-LOX metabolites sufficiently suppressed insulin-like growth factor II-induced 12-LOX expression and blocked cell cycle progression. On the basis of our findings, we think that the 15-LOX metabolites may inhibit epidermal hyperplasia in psoriasis by regulating 12-LOX expression. [Copyright &y& Elsevier]

Although there was no impairment in IL-2 secretion and proliferation of Fyn-deficient naïve CD4 cells after stimulation with antigen and antigen-presenting cells, stimulation of these cells with anti-CD3 and anti-CD28 revealed profound defects. Crosslinking of purified wild-type naïve CD4 cells with anti-CD3 activated Ick and initiated the signaling cascade downstream of Lck, including phosphorylation of ZAP-70, LAT, and PLC-γ1; calcium flux; and dephosphorylation and nuclear translocation of the nuclear factor of activated T cells (NFAT)p. All of these signaling events were diminished severely in Fyn-deficient naïve cells activated by CD3 crosslinking. Coaggregation of CD3 and CD4 reconstituted this Lck-dependent signaling pathway in Fyn-/- T cells. These results suggest that when signaling of naïve I cells is restricted to the T cell antigen receptor, Fyn plays an essential role by positive regulation of Lck activity. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) can modulate lymphocyte proliferation and function. One of the immunomodulatory functions of MSCs involves CD4+CD25+FoxP3+ regulatory T cells (Tregs), which negatively regulate inflammatory responses. MSC-mediated Treg induction is supposed to be regulated by mechanisms requiring both soluble and cell contact-dependent factors. Although the involvement of soluble factors has been revealed, the contact-dependent mechanisms in MSC-mediated Treg induction remain unclear. We attempted to identify molecule(s) other than secreted factors that are responsible for MSC-mediated Treg induction and to uncover the underlying mechanisms. Under in vitro Treg-inducing conditions, ICOSL expression in MSCs coincided with Treg induction in co-cultures of MSCs with CD4+ T cells. When cultured in a transwell plate, MSCs failed to induce Tregs. Neutralization or knockdown of ICOSL significantly reduced Tregs and their IL-10 release. ICOSL overexpression in MSCs promoted induction of functional Tregs. ICOSL-ICOS signaling promoted Treg differentiation from CD4+ T cells through activation of the phosphoinositide 3-kinase-Akt pathway. MSCs primed with Interleukin-1β significantly induced Tregs through ICOSL upregulation. We demonstrated that the Treg-inducing activity of MSCs is proportionate to their basal ICOSL expression. This study provides evidence that ICOSL expression in human MSCs plays an important role in contact-dependent regulation of MSC-mediated Treg induction. [ABSTRACT FROM AUTHOR]