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.