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J.Health Sci., 51(1), 62-69, 2005
17beta-Estradiol Primes Elicitation of Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide and Interferon-gamma in Mouse Macrophage Cell Line J774.1
Humitoshi Sakazaki, Ryoko Ido, Hitoshi Ueno, and Katsuhiko Nakamuro*
Division of Environmental Health, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
The effects of estrogenic compounds on nitric oxide (NO) production by macrophages were examined. 17beta-Estradiol promoted NO production triggered by lipopolysaccharide (LPS) and/or interferon (IFN)-gamma in the mouse macrophage cell line J774.1. Other estrogen-like substances such as estrone, 17alpha-ethynylestradiol and bisphenol A also enhanced NO synthesis, but this NO synthesis was not activated by Ca2+ ionophore A23187. RT-PCR analysis demonstrated induction of inducible nitric oxide synthase (iNOS) mRNA in J774.1 cells exposed to 17beta-estradiol. Although the estrogen receptor (ER)-antagonist ICI-182780 partially suppressed the promoting effect of 17beta-estradiol on NOS activity, there was little ER alpha detectable by RT-PCR from J774.1 cells. These results suggest that ERs may participate only partially in iNOS mRNA transcription in J774.1 cells and that 17beta-estradiol may act directly through other unknown intracellular signal transduction(s) that are activated by LPS and IFN-gamma.
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