PDF(Pubmed)
Abstract：
Bile acids are amphipathic molecules that are synthesized from cholesterol in the liver and facilitate intestinal absorption of lipids and nutrients. They are released into the small intestine upon ingestion of a meal where intestinal bacteria can modify primary into secondary bile acids. Bile acids are cytotoxic at high concentrations and have been associated with inflammatory diseases such as liver inflammation and Barrett\'s Oesophagus. Although bile acids induce pro-inflammatory signalling, their role in inducing innate immune cytokines and inflammation has not been fully explored to date. Here we demonstrate that the bile acids, deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) induce IL-1α and IL-1β secretion in vitro in primed bone marrow derived dendritic cells (BMDCs). The secretion of IL-1β was found not to require expression of NLRP3, ASC or caspase-1 activity; we can\'t rule out all inflammasomes. Furthermore, DCA and CDCA were shown to induce the recruitment of neutrophils and monocytes to the site of injection an intraperitoneal model of inflammation. This study further underlines a mechanistic role for bile acids in the pathogenesis of inflammatory diseases through stimulating the production of pro-inflammatory cytokines and recruitment of innate immune cells.
摘要：
胆汁酸是两亲分子,其由肝脏中的胆固醇合成并促进脂质和营养素的肠吸收。它们在摄入膳食后释放到小肠中，其中肠道细菌可以将初级胆汁酸修饰为次级胆汁酸。胆汁酸在高浓度下具有细胞毒性，并与炎症性疾病如肝脏炎症和Barrett食管有关。虽然胆汁酸诱导促炎信号，迄今为止，它们在诱导先天免疫细胞因子和炎症中的作用尚未得到充分探索。在这里，我们证明了胆汁酸，脱氧胆酸（DCA）和鹅去氧胆酸（CDCA）在体外诱导的骨髓来源的树突状细胞（BMDC）中诱导IL-1α和IL-1β分泌。发现IL-1β的分泌不需要NLRP3，ASC或caspase-1活性的表达；我们不能排除所有的炎性体。此外，DCA和CDCA显示诱导嗜中性粒细胞和单核细胞募集到腹膜内炎症模型的注射部位。该研究进一步强调了胆汁酸通过刺激促炎细胞因子的产生和先天免疫细胞的募集在炎性疾病的发病机理中的机制作用。
