Estrogen inhibits LPS-induced IL-6 production in macrophages partially via the nongenomic pathway

• Published in: Immunological investigations 2014-01, Vol.43 (7), p.693-704
• Main Authors: Liu, Limin, Zhao, Ying, Xie, Keming, Sun, Xiaodong, Jiang, Lili, Gao, Yuzhen, Wang, Zufeng
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - cytology; Estradiol - pharmacology; Estrogen; Estrogens - pharmacology; IL-6; Interleukin-6 - metabolism; Lipopolysaccharides - pharmacology; macrophage; Macrophages - drug effects; Macrophages - metabolism; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; nongenomic pathway; Protein Kinase Inhibitors - pharmacology; Serum Albumin, Bovine - pharmacology
• ISSN: 0882-0139; 1532-4311
• DOI: 10.3109/08820139.2014.917095

17β-estradiol (E2)-signaling is widely considered to be mediated through the transcription-regulating intracellular estrogen receptor (iER). In this study, using the cell-impermeable E2-BSA, we investigated the nongenomic effects of E2 on the IL-6 production, MAPK and transcription factor activation following LPS stimulation in mouse bone marrow-derived macrophages (BMMs). It was found that E2 normalized LPS-induced IL-6 production in BMMs. Although the increase in IL-6 production induced by LPS was also attenuated by E2-BSA treatment, the capacity of BMMs to produce the IL-6 cytokine remained higher than the control. In addition, the iER blocker, ICI 182780, did not abolish the total effects of E2 on LPS-stimulated IL-6 production capacity in BMMs. Furthermore, E2 and E2-BSA attenuated the LPS activation of p38 but not that of ERK1/2 and JNK. The p38 inhibitor, SB 203580, significantly reduced the LPS-induced IL-6 production. Moreover, E2 and E2-BSA inhibited LPS-induced activation of NF-κB. This inhibitory effect was associated with decreases in nuclear p65 protein levels. Taken together, these results indicate that E2 has an inhibitory effect on LPS-induced IL-6 production in BMMs through inhibition of p38 MAPK phosphorylation, and blockade of NF-κB activation. These effects are mediated at least in part via a nongenomic pathway.