Oestrogen exerts anti-inflammation via p38 MAPK/NF-κB cascade in adipocytes

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• 作者：Pan-wei Mu^a ; ¹ ; Ping Jiang^b ; ^c ; ¹ ; Man-man Wang^a ; Yan-ming Chen^a ; Shu-hui Zheng^b ; ^d ; Zhi Tan^b ; Wei Jiang^a ; Long-yi Zeng^a ; Ting-huai Wang^b ; ^{wangth@mail.sysu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：LPS ; lipopolysaccharides ; MCP-1 ; monocyte chemoattractant protein-1 ; E2 ; 17β-estradiol ; ERoestrogen ; receptor ; SB ; SB203580 ; PDTC ; pyrrolidine dithiocarbamate ; PTX ; pertussis toxin ; WM ; wortmannin ; PPT ; trisphenol ; DPN ; 2 ; 3-bis-(4-hydroxyphenyl)-propionitrile
• 刊名：Obesity Research & Clinical Practice
• 出版年：2016
• 出版时间：November-December 2016
• 年：2016
• 卷：10
• 期：6
• 页码：633-641
• 全文大小：1253 K

文摘

Oestrogen has anti-inflammatory property in obesity. However, the mechanism is still not defined.

Objective

To investigate the effect of oestrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1) production in adipocytes.

Methods

Lipopolysaccharides (LPS) was used to imitate inflammatory responses and monocyte chemotactic protein-1 (MCP-1) was selected as an inflammatory marker to observe. 17β-Estradiol (E₂), SB203580 (SB), pyrrolidine dithiocarbamate (PDTC), pertussis toxin (PTX), wortmannin (WM), p65 siRNA and p38 MAPK siRNA were pre-treated respectively or together in LPS-induced MCP-1. Then p38 MAPK and NF-κB cascade were silenced successively to observe the change of each other. Lastly, oestrogen receptor (ER) α agonist, ERβ agonist and ER antagonist were utilised.

Results

LPS-induced MCP-1 largely impaired by pre-treatment with E₂, SB, PDTC or silencing NF-κB subunit. E₂ inhibited LPS-induced MCP-1 in a time- and dose-dependent manner, which was related to the suppression of p65 translocation to nucleus. Furthermore, LPS rapidly activated p38 MAPK, while E₂ markedly inhibited this activation. It markedly attenuated LPS-stimulated p65 translocation to nucleus and MCP-1 production by transfecting with p38 MAPK siRNA or using p38 MAPK inhibitor. The oestrogen's inhibitory effect was mimicked by the ERα agonist, but not by the ERβ agonist. The inhibition of E₂ on p38 MAPK phosphorylation was prevented by ER antagonist.

Conclusions

E₂ inhibits LPS-stimulated MCP-1 in adipocytes. This effect is related to the inhibition of p38 MAPK/NF-κB cascade, and ERα appears to be the dominant ER subtype in these events.