通过激活缺氧诱导因子1α（HIF1α）信号通路促进肠道上皮细胞白细胞介素-18（IL-18）的产生。
promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway.
作者信息
Fagundes Raphael R, Bravo-Ruiseco Gabriela, Hu Shixian, Kierans Sarah J, Weersma Rinse K, Taylor Cormac T, Dijkstra Gerard, Harmsen Hermie J M, Faber Klaas Nico
机构信息
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
出版信息
Front Microbiol. 2023 Dec 14;14:1298304. doi: 10.3389/fmicb.2023.1298304. eCollection 2023.
INTRODUCTION
Intestinal epithelial cells produce interleukin-18 (IL-18), a key factor in promoting epithelial barrier integrity. Here, we analyzed the potential role of gut bacteria and the hypoxia-inducible factor 1α (HIF1α) pathway in regulating mucosal expression in inflammatory bowel disease (IBD).
METHODS
Mucosal samples from patients with IBD ( = 760) were analyzed for bacterial composition, levels and HIF1α pathway activation. Wild-type Caco-2 and CRISPR/Cas9-engineered Caco-2--null cells were cocultured with in a "Human oxygen-Bacteria anaerobic" system and analyzed by RNA sequencing.
RESULTS
Mucosal mRNA levels correlated positively with the abundance of mucosal-associated butyrate-producing bacteria, in particular , and with HIF1α pathway activation in patients with IBD. HIF1α-mediated expression of , either by a pharmacological agonist (dimethyloxallyl glycine) or , was abrogated in Caco-2--null cells.
CONCLUSION
Butyrate-producing gut bacteria like regulate mucosal expression in a HIF1α-dependent manner that may aid in mucosal healing in IBD.
引言
肠上皮细胞产生白细胞介素-18（IL-18），这是促进上皮屏障完整性的关键因素。在此，我们分析了肠道细菌和缺氧诱导因子1α（HIF1α）通路在炎症性肠病（IBD）中调节黏膜表达的潜在作用。
方法
对760例IBD患者的黏膜样本进行细菌组成、水平和HIF1α通路激活分析。将野生型Caco-2细胞和经CRISPR/Cas9技术构建的Caco-2基因敲除细胞在“人氧-细菌厌氧”系统中与共培养，并通过RNA测序进行分析。
结果
IBD患者黏膜mRNA水平与黏膜相关产丁酸细菌（特别是）的丰度以及HIF1α通路激活呈正相关。在Caco-2基因敲除细胞中，无论是通过药理学激动剂（二甲基草酰甘氨酸）还是，HIF1α介导的表达均被消除。
结论
像这样的产丁酸肠道细菌以HIF1α依赖的方式调节黏膜表达，这可能有助于IBD的黏膜愈合。
Zotero 插件