title: Estrogen inhibits LPS-induced IL-6 production in macrophages partially via the nongenomic pathway.
abstract: 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.
authors: Departments of Pathology and Pathophysiology, Medical College of Soochow University , Suzhou, Jiangsu , China , and.
authors: Limin
authors: L
authors: Liu
authors: Ying
authors: Y
authors: Zhao
authors: Keming
authors: K
authors: Xie
authors: Xiaodong
authors: X
authors: Sun
authors: Lili
authors: L
authors: Jiang
authors: Yuzhen
authors: Y
authors: Gao
authors: Zufeng
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
chemical_list: D004967:Estrogens; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C043090:estradiol-bovine serum albumin; C577686:interleukin-6, mouse; D012710:Serum Albumin, Bovine; D004958:Estradiol; D020928:Mitogen-Activated Protein Kinases
keywords: Estrogen; IL-6; macrophage; nongenomic pathway