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 TNFα expression at 8 days. However, TAK-242 alleviated decreased TNFα 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 TNFα 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.

中文翻译：

---

TLR4 可能是一种新的吲哚-3-乙酸受体，其参与调节 CYP1A1 和 TNFα 的表达，具体取决于 Caco-2 细胞的培养阶段。

大多数关于由肠道微生物群产生的吲哚衍生物（如 IAA）的研究都是基于与 AhR 结合会导致生物学反应的前提。我们之前发现 IAA 与多个受体结合，因此本研究旨在确定 IAA 的新受体并分析其作用机制。我们发现 TLR4 拮抗剂 TAK-242 在 3 小时不影响 IAA 诱导的 CYP1A1 表达增加，并在 8 天降低 TNFα 表达。然而，TAK-242 在 2 天时减轻了 IAA 诱导的 TNFα 表达降低，并通过在 8 天时抑制 JNK 活化来促进 IAA 诱导的 CYP1A1 表达增加。总之，TLR4 可能是一种新型 IAA 受体，其信号通路根据 Caco-2 细胞的培养阶段调节 CYP1A1 和 TNFα 的表达。此外，