We examined the effect of 17β-estradiol (E2) on the cytokine production by mouse splenocytes. The production of interferon-γ (IFN-γ) was enhanced by E2 stimulation. E2 increased the number of cells expressing IFN-γ and the IFN-γ mRNA expression level in the cells. There were low- and high-level cells expressing IFN-γ in the population. The natural killer (NK) cells and NKT cells were the low-level cells expressing IFN-γ, and the number of these cells was increased by E2 stimulation. In addition, it was suggested that the enhancing effect of IFN-γ production by E2 was mediated through estrogen receptor (ER) α, and ERβ agonist stimulated IFN-γ production. ERs are expressed on plasma membrane as well as in nucleus. The ligand specific to plasma membrane-associated ER (mER) enhanced the IFN-γ production. In conclusion, our results indicated that E2 up-regulated the IFN-γ production by mediating ERα, ERβ and mERs.
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