alpha-Naphthoflavone modulates inflammatory response in adipocytes-macrophages interaction through NF kappa B signaling

作者:Sun Yanmei; Xie Minghua; Huang Tingting; Zhang Xu; Lei Sicong; Shi Qun; Wang Suqing; Fan Cuifang*; Zhang Jie
来源:International Journal of Clinical and Experimental Pathology, 2014, 7(11): 7768-7774.

摘要

Objective: Our previous study demonstrated that alpha-naphthoflavone (alpha-NF) inhibits mouse 3T3-L1 pre-adipocytes differentiation via PPAR gamma, a key transcription factor in adipogenesis. Due to the critical role of inflammation in adipogenesis, we speculated that the suppression role of alpha-NF in adipogenesis might involve in modulation of cytokines secretion raised by adipocyte differentiation cocktail. Therefore, the present study aims to investigate the role of alpha-NF in modulating of inflammatory response during adipocytes differentiation and adipocyte-macrophage interaction. Methods: Conditioned medium from different doses of alpha-NF treated 10-day differentiated 3T3-L1 adipocytes were collected to culture RAW264.7 macrophages. Conditioned medium from activated macrophages and alpha-NF pre-treated macrophage were used to investigate the effects of alpha-NF in adipocytes differentiation. Cultured cells and medium were harvested for RT-PCR, Western blot and ELISA. Results: alpha-NF dose-dependently decreased TNF-alpha and IL-6 and increased IL-10 expression induced by IDM (Insulin, dexamethasone, isobutylmethylxanthine) in 3T3-L1 pre-adipocytes. Conditioned medium from alpha-NF treated 3T3-L1 differentiated cells inhibited inflammatory response in mouse macrophage cell line RAW264.7 in contrast to IDM control medium. NF gamma B activation elicited by IDM was suppressed by alpha-NF in a dose-response manner. Consequently, decreased TNF-alpha and increased IL-10 secretion, downstream targets of NF kappa B signaling pathway, were observed with alpha-NF in macrophages. Finally, Conditioned medium from alpha-NF pre-treated, LPS-activated macrophages ameliorated the suppression of 3T3-L1 adipogenesis by LPS activated macrophages. Conclusion: Our results suggest that alpha-NF regulates inflammation response in both adipocytes and macrophages and adipocyte-macrophage interaction which contributes to preadipocyte differentiation.