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Taurochenodeoxycholic acid mediates cAMP-PKA-CREB signaling pathway.

Abstract：

:Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.

journal_name

Chin J Nat Med

journal_title

Chinese journal of natural medicines

authors

Qi YC,Duan GZ,Mao W,Liu Q,Zhang YL,Li PF

doi

10.1016/S1875-5364(20)60033-4

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

898-906

issue

12

eissn

2095-6975

issn

1875-5364

pii

S1875-5364(20)60033-4

journal_volume

18

pub_type

杂志文章

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