Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease

BACKGROUND: Treatment of mild-moderate Alzheimer’s disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities of daily living (ADL) scores. METHODS: For this retrospective study, we examined banked CSF and plasma samples from a subset of AD subjects with CSF Aβ42 <600 ng/ml (biomarker-confirmed AD) at baseline (N = 19 resveratrol-treated and N = 19 placebo-treated). We utilized multiplex Xmap technology to measure markers of neurodegenerative disease and metalloproteinases (MMPs) in parallel in CSF and plasma samples. RESULTS: Compared to the placebo-treated group, at 52 weeks, resveratrol markedly reduced CSF MMP9 and increased macrophage-derived chemokine (MDC), interleukin (IL)-4, and fibroblast growth factor (FGF)-2. Compared to baseline, resveratrol increased plasma MMP10 and decreased IL-12P40, IL12P70, and RANTES. In this subset analysis, resveratrol treatment attenuated declines in mini-mental status examination (MMSE) scores, change in ADL (ADCS-ADL) scores, and CSF Aβ42 levels during the 52-week trial, but did not alter tau levels. CONCLUSIONS: Collectively, these data suggest that resveratrol decreases CSF MMP9, modulates neuro-inflammation, and induces adaptive immunity. SIRT1 activation may be a viable target for treatment or prevention of neurodegenerative disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT0150485

CCL17 Promotes Intestinal Inflammation in Mice and Counteracts Regulatory T Cell-Mediated Protection From Colitis.

BACKGROUND &amp; AIMS: Priming of T cells by dendritic cells (DCs) in the intestinal mucosa and associated lymphoid tissues helps maintain mucosal tolerance but also contributes to the development of chronic intestinal inflammation. Chemokines regulate the intestinal immune response and can contribute to pathogenesis of inflammatory bowel diseases. We investigated the role of the chemokine CCL17, which is expressed by conventional DCs in the intestine and is up-regulated during colitis. METHODS: Colitis was induced by administration of dextran sodium sulfate (DSS) to mice or transfer of T cells to lymphopenic mice. Colitis activity was monitored by body weight assessment, histologic scoring, and cytokine profile analysis. The direct effects of CCL17 on DCs and the indirect effects on differentiation of T helper (Th) cells were determined in vitro and ex vivo. RESULTS: Mice that lacked CCL17 (Ccl17(E/E) mice) were protected from induction of severe colitis by DSS or T-cell transfer. Colonic mucosa and mesenteric lymph nodes from Ccl17-deficient mice produced lower levels of proinflammatory cytokines. The population of Foxp3(+) regulatory T cells (Tregs) was expanded in Ccl17(E/E) mice and required for long-term protection from colitis. CCR4 expression by transferred T cells was not required for induction of colitis, but CCR4 expression by the recipients was required. CCL17 promoted Toll-like receptor-induced secretion of interleukin-12 and interleukin-23 by DCs in an autocrine manner, promoted differentiation of Th1 and Th17 cells, and reduced induction of Foxp3(+) Treg cells. CONCLUSIONS: The chemokine CCL17 is required for induction of intestinal inflammation in mice. CCL17 has an autocrine effect on DCs that promotes production of inflammatory cytokines and activation of Th1 and Th17 cells and reduces expansion of Treg cells

Atorvastatin Reduces Plasma Levels of Chemokine (CXCL10) in Patients with Crohn's Disease

BACKGROUND: In Crohn's disease high tissue expression and serum levels of chemokines and their receptors are known to correlate with disease activity. Because statins can reduce chemokine expression in patients with coronary diseases, we wanted to test whether this can be achieved in patients with Crohn's disease. METHODOLOGY/PRINCIPAL FINDINGS: We investigated plasma levels of chemokines (CCL2, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26, CXCL8, CXCL10) and endothelial cytokines (sP-selectin, sE-selectin, sICAM-3, thrombomodulin) in ten Crohn's disease patients before and after thirteen weeks' daily treatment with 80 mg atorvastatin. Of the 13 substances investigated, only CXCL10 was found to be significantly reduced (by 34%, p = 0.026) in all of the treated patients. Levels of CXCL10 correlated with C-reactive protein (r = 0.82, p<0.01). CONCLUSIONS/SIGNIFICANCE: CXCL10 is a ligand for the CXCR3 receptor, the activation of which results in the recruitment of T lymphocytes and the perpetuation of mucosal inflammation. Hence the reduction of plasma CXCL10 levels by atorvastatin may represent a candidate for an approach to the treatment of Crohns disease in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT0045454

Pseudomonas endophytica sp. nov., isolated from stem tissue of Solanum tuberosum L. in Spain

8 páginas, 2 tablas y 2 figuras. We, (the authors), acknowledge IDEBIO S. L. and Dr P. García-Benavides and Dr J. L. Palomo for their help and support. M.H.R.B. is the recipient of a JAE-Doc researcher contract from CSIC cofinanced by ERDF. We are grateful to V. Souza-Egipsy from ICA Electron Microscopy Service.A bacterial strain named BSTT44T was isolated in the course of a study of endophytic bacteria occurring in stems and roots of potato growing in a soil from Salamanca, Spain. The 16S rRNA gene sequence had 99.7% identity with respect to that of its closest relative, Pseudomonas psychrophila E-3T, and the next most closely related type strains were those of Pseudomonas fragi, with 99.6% similarity, Pseudomonas deceptionensis, with 99.2% similarity, and Pseudomonas lundensis, with 99.0% similarity; these results indicate that BSTT44T should be classified within the genus Pseudomonas. Analysis of the housekeeping genes rpoB, rpoD and gyrB confirmed its phylogenetic affiliation and showed identities lower than 92% in all cases with respect to the above-mentioned closest relatives. Cells of the strain bore one polar–subpolar flagellum. The respiratory quinone was Q-9.The major fatty acids were C16:0, C18:1v7c and summed feature 3 (C16:1v7c and/or C16:1v6c). The strain was oxidase-, catalase- and urease-positive and the arginine dihydrolase system was present, but tests for nitrate reduction, b-galactosidase production and aesculin hydrolysis were negative. It could grow at 35 8C and at pH 5–9.The DNA G+C content was 60.2 mol%. DNA–DNA hybridization results showed less than 48% relatedness with respect to the type strains of the four most closely related species. Therefore, the combined results of genotypic, phenotypic and chemotaxonomic analyses support the classification of strain BSTT44 into a novel species of the genus Pseudomonas, for which the name Pseudomonas endophytica sp. nov. is proposed. The type strain is BSTT44T (5LMG 28456T5CECT 8691T).Project CSI327A12-2Peer reviewe