Nonylphenol Attenuates SOCS3 Expression and M1 Polarization in Lipopolysaccharide-Treated Rat Splenic Macrophages.
Ecotoxicology and environmental safety(2019)
摘要
Endocrine disruptors interfere with normal sexual and reproductive development of numerous organisms. Widely used in several chemical and manufacturing industries, nonylphenol (NP), a potent xenoestrogen, has the potential to perturb immune system. Using rat splenic macrophages (SM Phi) as the model system, NP-modulation of lipopolysaccharide (LPS)-induced inflammatory response has been investigated. Our results demonstrate that NP (0.1-10 mu M) attenuates catalase activity, reactive oxygen species (ROS) generation and nitric oxide (NO) synthesis in LPS-treated SM Phi in vitro. NP inhibition of LPS-induced nuclear factor kappa B (NF-kappa B) activation and pro inflammatory cytokine gene expression corroborate well with attenuation of suppressor of cytokine signalling 3 (SOCS3). Besides, elevated expression of anti-inflammatory factors reveals inverse correlation with suppression of endotoxin-induced Ml polarization in NP pre-incubated cells. While LPS promotes, NP prevents ERK1/2 (extra cellular-signal-regulated kinase 1/2) phosphorylation and MEK-inhibitor abrogates SOCS3 expression and NO production suggesting involvement of ERK1/2 in NP inhibition of SOCS3 expression. Further, translational inhibitor cycloheximide prevents LPS-induced NF-kappa B activation indicating functional importance of de novo synthesis of SOCS3, at least in part, in toll-like receptor 4 (TLR4)-mediated inflammatory response. Collectively, present study provides evidence favouring participation of SOCS3 in NP modulation of inflammatory response in rat SM Phi.
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关键词
Endocrine disruption,Inflammation,NF-kappa 3,Cytokines,SOCS3,Nonylphenol
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