TLR4 may be a novel indole-3-acetic acid receptor that is implicated in the regulation of CYP1A1 and TNFα expression depending on the culture stage of Caco-2 cells
TLR4 may be a novel indole-3-acetic acid receptor that is implicated in the regulation of CYP1A1 and TNFα expression depending on the culture stage of Caco-2 cells
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DOI：
10.1093/bbb/zbab128
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发表时间：
2021-07-10
影响因子：
1.6
通讯作者：
Shimizu, Hidehisa
中科院分区：
文献类型：
--
作者：
Chowdhury, Md Mazharul Islam;Tomii, Ayame;Shimizu, Hidehisa
大多数关于吲哚衍生物如肠道微生物群产生的IAA的研究都是基于与AhR结合导致生物反应的前提。我们以前发现，IAA结合到一个以上的受体，因此，本研究的目的是确定一个新的受体IAA和分析其作用机制。我们发现TLR 4拮抗剂TAK-242在3 h时不影响IAA诱导的CYP 1A 1表达增加，在8天时不影响TNF α表达降低。然而，TAK-242在第2天缓解了IAA诱导的TNF α表达降低，并在第8天通过抑制JNK活化促进了IAA诱导的CYP 1A 1表达增加。总之，TLR 4可能是一种新的IAA受体，其信号传导通路根据Caco-2细胞的培养阶段调节CYP 1A 1和TNF α的表达。此外，我们的研究结果提供了重要的线索，阐明吲哚衍生物的作用机制，影响主机。
Most studies of indole derivatives such as IAA produced by intestinal microbiota have been based on the premise that binding to AhR leads to biological responses. We previously revealed that IAA binds to more than one receptor, and thus the present study aimed to identify a new receptor for IAA and analyze its mechanism of action. We found that the TLR4 antagonist TAK-242 did not affect the IAA-induced increase in CYP1A1 expression at 3 h and decreased TNF alpha expression at 8 days. However, TAK-242 alleviated decreased TNF alpha expression induced by IAA at 2 days and promoted IAA-induced increased CYP1A1 expression by inhibiting JNK activation at 8 days. Taken together, TLR4 may be a novel IAA receptor with signaling pathways that regulate CYP1A1 and TNF alpha expression depending on the culture stage of Caco-2 cells. Furthermore, our findings offer important clues for elucidating the action mechanisms of indole derivatives that affect hosts.