p38丝裂原活化蛋白激酶
自分泌信号
肿瘤坏死因子α
芳香烃受体
MAPK/ERK通路
旁分泌信号
化学
细胞因子
激酶
蛋白激酶A
细胞生物学
信号转导
癌症研究
内科学
内分泌学
生物
受体
医学
生物化学
转录因子
基因
作者
Kouichi Kurata,Katsunori Ishii,Yoshihito Koto,Kazuma Naito,Kana Yuasa,Hidehisa Shimizu
摘要
ABSTRACT Increased tumor necrosis factor α (TNFα) expression in intestinal epithelial cells (IECs) plays a major role in the development and progression of inflammatory bowel disease (IBD) and colorectal cancer (CRC). The present study aimed to clarify the relationship between TNFα and skatole, a tryptophan-derived gut microbiota metabolite. The aryl hydrocarbon receptor (AhR) antagonist CH223191 promoted, whereas the p38 inhibitor SB203580 suppressed the increase in TNFα mRNA and protein expression induced by skatole in intestinal epithelial Caco-2 cells. The c-Jun N-terminal kinase (JNK) inhibitor SP600125 repressed only the increased TNFα protein expression, whereas the extracellular signal-regulated kinase (ERK) pathway inhibitor U0126 did not affect increased TNFα expression at any level. A neutralizing antibody against TNFα partially inhibited skatole-induced cell death. Overall, these results suggested that TNFα expression is increased by the concerted actions of skatole-activated p38 and JNK, and that TNFα exerts autocrine/paracrine actions on IECs despite partial suppression by activated AhR. Therefore, skatole might play an important role in the development and progression of IBD and CRC via increased TNFα expression.
科研通智能强力驱动
Strongly Powered by AbleSci AI