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

Background: 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. 17 beta-Estradiol (E-2), 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-kappa B cascade were silenced successively to observe the change of each other. Lastly, oestrogen receptor (ER) alpha agonist, ER beta agonist and ER antagonist were utilised. Results: LPS-induced MCP-1 largely impaired by pre-treatment with E-2, SB, PDTC or silencing NF-kappa B subunit. E-2 inhibited LPS- induced MCP-1 in a time- and dose-dependent manner, which was related to the suppression of p65 translocation tonucleus. Furthermore, LPS rapidly activated p38 MAPK, while E-2 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 ER alpha agonist, but not by the ER beta agonist. The inhibition of E-2 on p38 MAPK phosphorylation was prevented by ER antagonist. Conclusions: E-2 inhibits LPS-stimulated MCP-1 in adipocytes. This effect is related to the inhibition of p38 MAPK/NF-kappa B cascade, and ER alpha appears to be the dominant ER subtype in these events. (C) 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.