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Urinary tract infections are a severe public health problem. The emergence and spread of antimicrobial resistance among uropathogens threaten to further compromise the quality of life and health of people who develop acute and recurrent upper and lower urinary tract infections. The host defense mechanisms that prevent invasive bacterial infection are not entirely delineated. However, recent evidence suggests that versatile innate immune defenses play a key role in shielding the urinary tract from invading uropathogens. Over the last decade, considerable advances have been made in defining the innate mechanisms that maintain immune homeostasis in the kidney and urinary tract. When these innate defenses are compromised or dysregulated, pathogen susceptibility increases. The objective of this review is to provide an overview of how basic science discoveries are elucidating essential innate host defenses in the kidney and urinary tract. In doing so, we highlight how these findings may ultimately translate into the clinic as new biomarkers or therapies for urinary tract infection., Author(s): Christina Ching [sup.1] [sup.2] [sup.3] , Laura Schwartz [sup.1] [sup.2] , John David Spencer [sup.1] [sup.2] [sup.4] , Brian Becknell [sup.1] [sup.2] [sup.4] Author Affiliations: (1) grid.240344.5, 0000 0004 [...]

Urinary tract infections (UTIs) are generally considered a disease of women. However, UTIs affect females throughout the lifespan, and certain male populations (including infants and elderly men) are also susceptible. Epidemiologically, pyelonephritis is more common in women but carries increased morbidity when it does occur in men. Among children, high-grade vesicoureteral reflux is a primary risk factor for upper-tract UTI in both sexes. However, among young infants with UTI, girls are outnumbered by boys; risk factors include posterior urethral valves and lack of circumcision. Recent advances in mouse models of UTI reveal sex differences in innate responses to UTI, which vary somewhat depending on the system used. Moreover, male mice and androgenized female mice suffer worse outcomes in experimental pyelonephritis; evidence suggests that androgen exposure may suppress innate control of infection in the urinary tract, but additional androgen effects, as well as non-hormonal sex effects, may yet be specified. Among other intriguing directions, recent experiments raise the hypothesis that the postnatal testosterone surge that occurs in male infants may represent an additional factor driving the higher incidence of UTI in males under 6 months of age. Ongoing work in contemporary models will further illuminate sex- and sex-hormone-specific effects on UTI pathogenesis and immune responses., Author(s): Clayton D. Albracht [sup.1] , Teri N. Hreha [sup.1] , David A. Hunstad [sup.1] [sup.2] Author Affiliations: (1) grid.4367.6, 0000 0001 2355 7002, Department of Pediatrics, Washington University School [...]

A crude extract from Acanthopanax senticosus (AS) has drawn increased attention because of its potentially beneficial activities, including anti-fatigue, anti-stress, anti-gastric-ulcer, and immunoenhancing effects. We previously reported that AS crude extract exerts anti-inflammatory activity through blockade of monocytic adhesion to endothelial cells. However, the underlying mechanisms remained unknown, and so this study was designed to investigate the pathways involved. It was confirmed that AS extract inhibited lipopolysaccharide (LPS)-induced adhesion of monocytes to endothelial cells, and we found that whole extract was superior to eleutheroside E, a principal functional component of AS. A series of PCR experiments revealed that AS extract inhibited LPS-induced expression of genes encoding lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) in THP-1 cells. Consistently, protein levels and cell surface expression of LFA-1 and Mac-1 were noticeably reduced upon treatment with AS extract. This inhibitory effect was mediated by the suppression of LPS-induced degradation of IκB-α, a known inhibitor of nuclear factor-κB (NF-κB). In conclusion, AS extract exerts anti-inflammatory activity via the suppression of LFA-1 and Mac-1, lending itself as a potential therapeutic galenical for the prevention and treatment of various inflammatory diseases. Key words: Acanthopanax senticosus extract, LFA-1, Mac-1, I-κB, cell adhesion. L'extrait brut d Acanthopanax senticosus (AS) a ete l'objet d'une attention croissante a cause des ses activites benefiques potentielles, incluant des effets antifatigue, anti-stress, contre les ulceres gastriques et immuno-stimulateurs. Nous avions precedemment rapporte que l'extrait brut d'AS exerce une activite anti-inflammatoire par le blocage de l'adhesion des monocytes aux cellules endotheliales. Cependant, les mecanismes sous-jacents demeurent inconnus; consequemment, l'etude presente a ete concue afin d'examiner les sentiers impliques. Il a ete confirme que l'extrait d'AS inhibait l'adhesion des monocytes aux cellules endotheliales induite par le LPS, et nous avons trouve que l'extrait total etait superieur a l'eleutheroside E, la principale composante fonctionnelle d'AS. Une serie d'experiences par PCR a revele que l'extrait d'AS inhibait l'expression induite par le LPS de genes codant LFA-1 (lymphocyte function-associated antigen-1) et Mac-1 (macrophage-1 antigen) chez les cellules THP-1. En consequence, les niveaux proteiques et l'expression a la surface cellulaire de LFA-1 et Mac-1 etaient reduits de maniere importante a la suite du traitement a l'extrait d'AS. L'effet inhibiteur etait dependait de la suppression de la degradation d'IκB-α induite par le LPS, un inhibiteur connu du facteur nucleaire NF-κB. En conclusion, l'extrait d'AS exerce une activite antiinflammatoire par la suppression de LFA-1 et de Mac-1, ce qui en fait un medicament galenique potentiel pour la prevention et le traitement de differentes maladies inflammatoires. [Traduit par la Redaction] Mots-cles: extrait d 'Acanthopanax senticosus, LFA-1, Mac-1, IκB, adhesion cellulaire., Introduction Acanthopanax senticosus (AS; Siberian ginseng) belongs to the plant family Araliaceae and has been widely used as a traditional medicinal plant in East Asia (Davydov and Krikorian 2000). In [...]

Peroxisome proliferator-activated receptor-[gamma] (PPAR[gamma]) agonists, exemplified by the thiazolidinediones (TZDs), have been used extensively for their beneficial effects to improve insulin sensitivity and lipid metabolism in type 2 diabetic patients. PPAR[gamma] receptors are part of the steroid hormone nuclear receptor family and, when activated by agonist binding, can affect numerous target genes expressing PPAR response elements. Results from experimental studies and a limited number of studies in humans suggest that PPAR[gamma] agonists have manifold effects beyond those on dysmetabolic syndrome. These potentially beneficial actions are mediated via renal parenchymal and infiltrating cells and modulate fibrotic, inflammatory, immune, proliferative, reactive oxygen and mitochondrial injury pathways. Thus, the potential benefits of TZDs in chronic kidney disease impact numerous pathogenic pathways. This review will focus on evidence of the effects of TZDs in nondiabetic chronic kidney disease in experimental and human disease settings. Keywords PPAR[gamma] * Chronic kidney disease * Sclerosis * Podocyte * Proteinuria, Introduction Peroxisome proliferator-activated receptor-[gamma] (PPAR[gamma]) agonists, exemplified by the thiazolidinediones (TZDs), are used to improve insulin sensitivity and dyslipidemia in type 2 diabetic patients [1-3]. PPAR[gamma] receptors are part of [...]

Single gene mutations in [beta] integrins can account for functional defects of individual cells of the hematopoietic system. In humans, mutations in [[beta].sub.2] integrin lead to leukocyte adhesion deficiency (LAD) [...]

Author(s): Markus Hafner [1]; Anton Schmitz [1]; Imke Grüne [1]; Seergazhi G. Srivatsan [1]; Bianca Paul [2]; Waldemar Kolanus [2]; Thomas Quast [2]; Elisabeth Kremmer [3]; Inga Bauer [1]; Michael [...]

Author(s): Bernhard Fuss [1, 2]; Thomas Becker [1, 2]; Ingo Zinke [1, 2]; Michael Hoch (corresponding author) [1] In metazoans, the insulin signalling pathway has a key function in regulating [...]

Purpose. Leukocyte recruitment from blood vessels to inflamed tissues is the central step in the process of inflammation. This may cause damage of the inflamed tissues in the case of [...]

Author(s): Aisha Siddiqa [1, 2]; Jennifer C. Sims-Mourtada [1, 2]; Liliana Guzman-Rojas [1, 2]; Roberto Rangel [1, 2]; Christiane Guret [3]; Vicente Madrid-Marina [4]; Yan Sun [2]; Hector Martinez-Valdez (corresponding [...]

Byline: Jayeeta. Banerjee Studies on antibody were documented as early as in 1890. They are proteins found in blood or other body fluid of vertebrates, and are used by the [...]

I. INTRODUCTION Small GTP-binding proteins (G proteins) are monomeric G proteins with molecular masses of 20--40 kDa. The Ha-Ras and Ki-Ras genes were first discovered as the v-Ha-Ras and v-Ki-Ras [...]