title: 17beta-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. 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.
authors.affiliation: Department of Dermatology, Teikyo University, School of Medicine, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000494:pharmacology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D012739:Gonadal Steroid Hormones; D007328:Insulin; D050832:Interferon-Stimulated Gene Factor 3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C079868:gamma interferon activation factor; D014443:Tyrosine; D004958:Estradiol; D007371:Interferon-gamma; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2