Taurochenodeoxycholic acid mediates cAMP-PKA-CREB signaling pathway.
10.1016/S1875-5364(20)60033-4
- Author:
You-Chao QI
1
,
2
;
Guo-Zhen DUAN
3
;
Wei MAO
1
,
2
;
Qian LIU
1
,
2
;
Yong-Liang ZHANG
4
;
Pei-Feng LI
1
,
5
Author Information
1. College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China
2. Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Hohhot 010018, China.
3. College of Forestry, Inner Mongolia Agricultural University, Hohhot 010018, China.
4. Immunology Progamme, Life Sciences Institute, National University of Singapore, Singapore 117597, Singapore.
5. Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Hohhot 010018, China. Electronic address: lipeifengnmg@126.com.
- Publication Type:Journal Article
- Keywords:
Anti-inflammation;
Cyclic adenosine monophosphate;
Protein kinase A;
TGR5 receptor;
Taurochenodeoxycholic acid;
cAMP response element binding
- MeSH:
Animals;
Cell Line;
Cyclic AMP/metabolism*;
Cyclic AMP Response Element-Binding Protein/metabolism*;
Cyclic AMP-Dependent Protein Kinases/metabolism*;
Cytokines/metabolism*;
Humans;
Inflammation;
Macrophages;
Rats;
Receptors, G-Protein-Coupled/metabolism*;
Signal Transduction/drug effects*;
Taurochenodeoxycholic Acid/pharmacology*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2020;18(12):898-906
- CountryChina
- Language:English
-
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.
