Estrogen inhibits lipopolysaccharide-induced tumor necrosis factor-alpha release from murine macrophages.
During their reproductive years, female have a lower risk for atherosclerosis as compared with age-matched males, although the mechanisms behind this are not clearly understood. Cytokines, including TNF-alpha play an important role in the pathogenesis of atherosclerosis. We therefore evaluated whether or not there was any difference between 17 beta-estradiol and testosterone in modulating TNF-alpha release from murine bone marrow-derived macrophages (BMM) in vitro. Cells were incubated with or without physiological concentrations (10(-10)-10(-8) M) of 17 beta-estradiol or testosterone for 48 h, followed by an additional 6 h in the absence or presence of lipopolysaccharide (LPS; 10 micrograms/ml). The amount of TNF-alpha released into the culture medium was determined with radioimmunoassay. We found that 17 beta-estradiol or testosterone alone did not affect TNF-alpha release from BMM as compared to untreated controls. Preincubation with 17 beta-estradiol significantly inhibited LPS-induced TNF-alpha release by 18.15% (p < 0.05). 25.28% (p < 0.05) and 40.83% (p < 0.01) for 10(-10), 10(-9) and 10(-8) M of 17 beta-estradiol, respectively, as compared to LPS alone. In contrast, testosterone tested for 3 concentrations did not significantly effect TNF-alpha release induced by LPS. The results indicate that 17 beta-estradiol, but not testosterone, inhibits TNF-alpha release from LPS-stimulated macrophages, which may be one of the mechanisms by which estrogen protects against atherosclerosis.
Zhang
X
X
Laboratory of Molecular Biology, Shanxi Medical University, Taiyuan, P.R. China. zdqiao@public.ty.sx.cn
Wang
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L
Zhang
H
H
Guo
D
D
Qiao
Z
Z
Qiao
J
J
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D013739:Testosterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D004958:Estradiol