title: Interferon gamma induces steroid sulfatase expression in human keratinocytes.
abstract: Steroid sulfatase (STS) plays an important role in steroid metabolism in which estrogens and dehydroepiandrosterone (DHEA) are produced from their sulfates. However, little is known about the transcriptional regulation of the STS gene in keratinocytes. Since keratinocytes are thought to be a primary target of interferon gamma (IFNγ) in inflammatory and immune responses, we assessed the effects of this cytokine upon STS gene expression in the human keratinocyte cell line SVHK and in normal human keratinocytes (NHEK). Stimulation of SVHK cells with 50 ng/mL of IFNγ for 24 h induced an approximately three-fold increase in STS activity and in its mRNA levels compared to non-treated cells. IFNγ treatment also induced an approximately 1.5-fold increase in STS mRNA levels in NHEK cells. This induction was completely inhibited by treatment with phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, and by the nuclear factor-kappa B (NF-κB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). These data suggest that activation of the PI 3-kinase signal transduction pathway mediates induction of STS gene expression by IFNγ through activation of NF-κB. The anti-inflammatory agent dexamethasone inhibited IFNγ induction of STS gene expression, suggesting involvement of a glucocorticoid receptor in the regulation of STS gene expression in keratinocytes. Regulation of STS gene expression in skin as a novel target of drugs for therapy of psoriasis in the skin is discussed.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hattori
authors.forename: Nozomi
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Tamura
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases; D043266:Steryl-Sulfatase