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Polarized macrophages treated with nonylphenol differently regulate lipopolysaccharide‐induced sepsis

Nonylphenol (NP) as well‐known “endocrine disrupter” influences sexual and reproductive development. Here, we investigated the effect of NP on M1‐/M2‐type macrophages and their role in lipopolysaccharide (LPS)‐induced sepsis. Polarized macrophages of M1‐ and M2‐types were obtained by the treatment with LPS and interleukin‐4 (IL‐4) to bone marrow‐derived macrophages (BMDM), respectively. Coincubation of M1‐macrophages with NP decreased COX‐2, iNOS, IL‐6, and TNF‐α expression but no changes were detected in the production of nitric oxide (NO). Survival probability of LPS‐induced sepsis mice was enhanced by the injection of NP‐treated BMDM as compared to the injection of NP‐untreated control BMDM. In the meanwhile, the expression of arginase 1(Arg1), a marker for M2‐polarized macrophages was increased by the stimulation with LPS in BMDM. Arg1 expression was also enhanced by the treatment with IL‐4 in BMDM, which was reduced by the coincubation with NP. Survival probability of LPS‐induced sepsis mice was decreased by the injection of BMDM treated with IL‐4 and NP as compared to the injection of IL‐4‐treated BMDM. It suggests that NP might inhibit macrophage function and the polarization to M2‐macrophages. Taken together, data demonstrate that NP could differently affect immune responses of polarized macrophages resulted in the modulation of LPS‐induced sepsis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2081–2089, 2016.