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

Abstract

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. 17β-estradiol inhibited interferon-γ-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 17β-estradiol. Interferon-γ-induced protein of 10 kDa production was also inhibited by anti-estrogens, ICI 182 780 and tamoxifen, and membrane-impermeable bovine serum albumin-conjugated 17β-estradiol, suggesting the effects via membrane estrogen receptor, whereas 17α-estradiol, progesterone, and dihydrotestosterone had no effects. 17β-estradiol and bovine serum albumin-conjugated 17β-estradiol suppressed interferon-γ-induced transcription through the interferon-stimulated response element and signal transducer and activator of transcription 1α binding to interferon-stimulated response element. 17β-estradiol and bovine serum albumin-conjugated 17β-estradiol suppressed interferon-γ-induced tyrosine phosphorylation of signal transducer and activator of transcription 1α, and Janus tyrosine kinase I and 2. 17β-estradiol-mediated suppression on the interferon-γ-induced signal transducer and activator of transcription 1α activation and interferon-induced protein of 10 kDa synthesis was counteracted by adenylate cyclase inhibitor SQ22536. 17β-estradiol, bovine serum albumin-conjugated 17β-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 17β-estradiol bound to the surface of keratinocytes, and mRNA for estrogen receptor β but not for estrogen receptor was detected in keratinocytes. These results suggest that 17β-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-γ-induced signal transducer and activator of transcription 1α activation and interferon-induced protein of 10 kDa synthesis.