17beta-estradiol inhibits the production of interferon-induced protein of 10 kDa by human keratinocytes.

The natural course of psoriasis is often modulated during pregnancy, indicating the regulatory effect of estrogen or progesterone on psoriasis. Interferon-induced protein of 10 kDa chemoattracts T helper 1 cells, and interferon-induced protein of 10 kDa production by keratinocytes is enhanced in psoriatic skin lesions. We examined in vitro effects of sex hormones on the interferon-induced protein of 10 kDa production by human keratinocytes. 17beta-estradiol inhibited interferon-gamma-induced interferon-induced protein of 10 kDa secretion, mRNA expression, and promoter activity. Interferon-stimulated response element on the promoter was responsible for the inhibition by 17beta-estradiol. Interferon-gamma-induced protein of 10 kDa production was also inhibited by anti-estrogens, ICI 182 780 and tamoxifen, and membrane-impermeable bovine serum albumin-conjugated 17beta-estradiol, suggesting the effects via membrane estrogen receptor, whereas 17alpha-estradiol, progesterone, and dihydrotestosterone had no effects. 17beta-estradiol and bovine serum albumin-conjugated 17beta-estradiol suppressed interferon-gamma-induced transcription through the interferon-stimulated response element and signal transducer and activator of transcription 1alpha binding to interferon-stimulated response element. 17beta-estradiol and bovine serum albumin-conjugated 17beta-estradiol suppressed interferon-gamma-induced tyrosine phosphorylation of signal transducer and activator of transcription 1alpha, and Janus tyrosine kinase 1 and 2. 17beta-estradiol-mediated suppression on the interferon-gamma-induced signal transducer and activator of transcription 1alpha activation and interferon-induced protein of 10 kDa synthesis was counteracted by adenylate cyclase inhibitor SQ22536. 17beta-estradiol, bovine serum albumin-conjugated 17beta-estradiol, ICI 182 780, and tamoxifen increased intracellular 3',5'-adenosine cyclic monophosphate level by activating adenylate cyclase in keratinocytes. Fluorescein isothiocyanate-labeled bovine serum albumin-conjugated 17beta-estradiol bound to the surface of keratinocytes, and mRNA for estrogen receptor beta but not for estrogen receptor alpha was detected in keratinocytes. These results suggest that 17beta-estradiol may interact with the membrane receptor on keratinocytes and generate 3',5'-adenosine cyclic monophosphate by activating adenylate cyclase, which may lead to the inhibition of interferon-gamma-induced signal transducer and activator of transcription 1alpha activation and interferon-induced protein of 10 kDa synthesis.