1. Estrogen inhibits LPS-induced IL-6 production in macrophages partially via the nongenomic pathway.
- Author
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Liu, Limin, Zhao, Ying, Xie, Keming, Sun, Xiaodong, Jiang, Lili, Gao, Yuzhen, and Wang, Zufeng
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ESTROGEN ,CELLULAR signal transduction ,INTERLEUKIN-6 ,MACROPHAGES ,TRANSCRIPTION factors ,ESTRADIOL ,ESTROGEN receptors - Abstract
17β-estradiol (E
2 )-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. [ABSTRACT FROM AUTHOR]- Published
- 2014
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