Effect of estrogens on the interferon-gamma producing cell population of mouse splenocytes.

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