title: Opposing effects of estradiol and progesterone on the oxidative stress-induced production of chemokine and proinflammatory cytokines in murine peritoneal macrophages.
abstract: In inflammatory and oxidative liver injury, virus proteins and reactive oxygen species are involved in the regulation of proinflammatory cytokine production by macrophages. This study investigated the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stress-stimulated production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, macrophage inflammatory protein (MIP)-2, and macrophage chemotactic protein (MCP)-1 by peritoneal macrophages isolated from male and female mice. E2 inhibited the cytokine production of TNF-alpha, IL-1beta, MIP-2, and MCP-1 by the unstimulated macrophages from males and females, which was then further stimulated by progesterone. The exposure to hydrogen peroxide in the macrophages from both sexes induced the production of cytokine. The hydrogen peroxide-stimulated cytokine production was suppressed by E2 and enhanced by progesterone. The sex hormone effects on the unstimulated and stimulated macrophages were blocked by their receptor antagonists and showed no significant difference between male and female subjects. These findings suggest that E2 may play a favorable role in the course of persistent liver injury, by inhibiting proinflammatory cytokine production, which, in addition, progesterone may counteract the favorable E2 effects through their receptors.
authors.affiliation: Department of Digestive and Cardiovascular Medicine, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Huiwei
authors.initials: H
authors.lastname: Huang
authors.forename: Jianghong
authors.initials: J
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Eriko
authors.initials: E
authors.lastname: Aoyagi
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Takenaka
authors.forename: Tatuzo
authors.initials: T
authors.lastname: Itagaki
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Sannomiya
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tamaki
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shono
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shimizu
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D003864:Depression, Chemical; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018384:Oxidative Stress / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology* / Q000502:physiology; D013268:Stimulation, Chemical
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D011374:Progesterone; D004958:Estradiol