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Biosci Biotechnol Biochem ; 85(9): 2011-2021, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34245564

RESUMO

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.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Ácidos Indolacéticos/metabolismo , Receptor 4 Toll-Like/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Células CACO-2 , Ativação Enzimática , Humanos , MAP Quinase Quinase 4/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
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