title: Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin: A special reference to the nested gene LYNX1.
abstract: A novel nicotinic acetylcholine (ACh) receptor (nAChR)-mediated transduction pathway, regulating keratinocyte function, has been elucidated in studies of secreted mammalian Ly6/urokinase plasminogen activator receptor-related protein (SLURP)-1 and -2. SLURPs are members of Ly6/neurotoxin superfamily (Ly6SF) of proteins containing the unique three-finger domain in their three-dimensional structure. Some endogenously expressed Ly6SF proteins (such as LYNX1, SLURP-1, and SLURP-2) modulate the function of nAChR, either as allosteric and/or orthosteric modulators, or as antagonists. Although the expression and functions of SLURP-1 and SLURP-2 in keratinocytes are well documented, the expression and the modes of action of LYNX1 in keratinocytes are unknown. Additionally, a particular hybrid transcript, LYNX1-SLURP2, which contains both LYNX1 and SLURP-2 sequences, with unknown function, has been reported. Furthermore, although SLURP2 is a gene strongly induced in psoriatic skin lesions, the mechanisms controlling SLURP2 expression are largely unknown. To better understand the function of nAChRs in keratinocytes, we investigated the expression profiles of LYNX1, LYNX1-SLURP-2, and SLURP-2 in keratinocytes under various inflammatory conditions. We found that keratinocytes express LYNX1 and SLURP2, but not LYNX1-SLURP2, at mRNA and protein levels. IL-22 treatment increased SLURP2 expression in keratinocytes, but this effect was completely abolished by IFN-γ. Furthermore, the IL-22-induced up-regulation of SLURP2 was completely suppressed by the inhibitor or siRNA for STAT3, a major transcriptional factor downstream of IL-22. These findings provide new insights into the nAChR-mediated regulatory mechanism of SLURP-2 expression in keratinocytes.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan. Electronic address: moriwaki-ys@pha.keio.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Moriwaki
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Takada
authors.affiliation: Molecular Diagnostics Project, Kanagawa Cancer Center Research Institute, Kanagawa, Japan.
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmacy, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawashima
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan. Electronic address: misawa-hd@pha.keio.ac.jp.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D034741:RNA, Small Interfering; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D014158:Transcription, Genetic; D000097043:Interleukin-22
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D005419:Flavonoids; D058851:GPI-Linked Proteins; D007378:Interleukins; D034741:RNA, Small Interfering; D050791:STAT Transcription Factors; D000097043:Interleukin-22; C485626:LYNX1 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Acetylcholine receptor; IL-22; Keratinocyte; LYNX1; SLURP