Investigating immunomodulating mechanisms of probiotics

益生菌是“活生生的微生物，当给予足够的量时，会给宿主带来健康益处”。越来越多的研究为益生菌在缓解几种炎症性疾病方面的功效和效率提供了科学证据。然而，益生菌促进健康的具体机制，特别是它们的抗炎特性仍然知之甚少。本研究旨在探讨益生菌的信号转导和分子免疫调节机制。我们已经证明，鼠李糖乳杆菌的益生菌菌株是产生G-CSF的有效诱导剂，G-CSF可以抑制激活的巨噬细胞中促炎症细胞因子肿瘤坏死因子(TNF)的产生。我们推测，鼠李糖优先在单核/巨噬细胞中诱导G-CSF，G-CSF是介导巨噬细胞和树突状细胞免疫调节作用的关键抗炎细胞因子。针对这一假说，我们提出了四个具体的研究目标：1)研究鼠李糖激活的巨噬细胞产生G-CSF的信号机制；2)研究G-CSF对巨噬细胞的影响；3)研究G-CSF调节巨噬细胞活化的机制；4)研究G-CSF对树突状细胞的作用。

Probiotics are 'living micro-organisms that when administered in adequate amounts confer a health benefit to the host'. An increasing number of studies provide scientific evidence for the efficacy and efficiency of probiotics in alleviating several inflammatory diseases. However, the specific mechanisms by which probiotic bacteria contribute to health, and, especially, their anti-inflammatory properties remain poorly understood. This research program is to investigate the signaling and molecular immunomodulatory mechanisms of probiotics. We have shown that probiotic strains of Lactobacillus rhamnosus are potent inducers of G-CSF production, which suppresses production of the pro-inflammatory cytokine tumor necrosis factor (TNF) in activated macrophages. We hypothesize that L. rhamnosus preferentially induces G-CSF in monocytes/macrophages, which is a key anti-inflammatory cytokine mediating immunomodulatory effects on macrophages and dendritic cells. To address the hypothesis, we propose the following four specific research objectives: 1) Investigating the signaling mechanism of G-CSF production in L. rhamnosus-activated macrophages, 2) Investigating the effect of G-CSF on macrophages, 3) Investigating the mechanism of G-CSF in regulating macrophage activation and 4) Investigating the role of G-CSF on dendritic cells.