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Immunopharmacol Immunotoxicol. 2019 Feb;41(1):172-177. doi: 10.1080/08923973.2019.1568451. Epub 2019 Mar 21.

Sinomenine regulates CD14/TLR4, JAK2/STAT3 pathway and calcium signal via α7nAChR to inhibit inflammation in LPS-stimulated macrophages.

Author information

1
a Department of Immunology, Institute of Clinical Pharmacology , Guangzhou University of Chinese Medicine , Guangzhou , P.R. China.
2
b Faculty of Chinese Medicine , Macau University of Science and Technology, the State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology) , Taipa , P.R. China.
3
c International Institute of Translation Chinese Medicine , Guangzhou University of Chinese Medicine , Guangzhou , P.R. China.

Abstract

Objective: To investigate the cellular mechanism that sinomenine (SIN) inhibits inflammation in macrophages induced by LPS through α7 nicotinic acetylcholine receptor (α7nAChR). Materials and methods: RAW264.7 cells were stimulated with LPS and treated by SIN or nicotine (Nic). A selective antagonist of α7nAChR, α-bungarotoxin (BTX) was used to block α7nAChR. AG490 was used to inhibit JAK2 activation. ELISA was performed to detect the levels of TNF-α and MCP-1. Western blotting was used to analyze the expression of MIF, MMP-9, CD14, TLR4, STAT3 and p-STAT3. Intracellular-free calcium level was measured by Fluorescent probe fluo-3/AM Results: SIN inhibited the production of TNF-α, MCP-1, MIF, and MMP-9, decreased the expression of CD14 and TLR4, and inhibited the release of intracellular-free calcium from intracellular stores in RAW 264.7 cells stimulated by LPS. JAK-specific inhibitor AG490 attenuated the inhibitory effect of SIN on TNF-α. SIN increased the phosphorylation of STAT3. And the above effects of SIN were attenuated by antagonist of α7nAChR. Conclusions: SIN can decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages.

KEYWORDS:

Sinomenine; anti-inflammation; signaling pathway; target; α7 nicotinic acetylcholine receptor

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