title: Visfatin enhances the production of cathelicidin antimicrobial peptide, human β-defensin-2, human β-defensin-3, and S100A7 in human keratinocytes and their orthologs in murine imiquimod-induced psoriatic skin.
abstract: Psoriasis, a chronic inflammatory dermatosis, is frequently associated with metabolic disorders, suggesting that adipokines are involved in its pathogenesis. We recently reported that the adipokine visfatin activates NF-κB and STAT3 in keratinocytes. Antimicrobial peptide expression is enhanced in psoriatic lesions and may promote disease development. Here, we investigated the effects of visfatin on antimicrobial peptide expression. In vitro, visfatin enhanced basal and tumor necrosis factor-α (TNF-α)-induced mRNA expression and secretion of cathelicidin antimicrobial peptide (CAMP), and enhanced TNF-α-induced human β-defensin-2 (hBD-2), hBD-3, and S100A7 mRNA expression and secretion in human keratinocytes. siRNAs targeting CCAAT/enhancer-binding protein-α (C/EBPα) suppressed visfatin-induced and visfatin plus TNF-α-induced CAMP production. siRNAs targeting NF-κB p65 and STAT3 suppressed visfatin plus TNF-α-induced hBD-2 and S100A7 production. siRNAs targeting c-Jun and STAT3 suppressed visfatin plus TNF-α-induced hBD-3 production. Visfatin and/or TNF-α enhanced C/EBP transcriptional activity and C/EBPα phosphorylation, which were suppressed by p38 mitogen-activated protein kinase (MAPK) inhibition. Visfatin and/or TNF-α induced p38 MAPK phosphorylation. Visfatin increased mRNA and protein expression of CAMP, hBD-2, hBD-3, and S100A7 orthologs in murine imiquimod-treated skin, mimicking psoriasis. In conclusion, visfatin enhances CAMP, hBD-2, hBD-3, and S100A7 production in human keratinocytes and their orthologs in murine imiquimod-treated psoriatic skin. Visfatin may potentiate the development of psoriasis via antimicrobial peptides.
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Carren S
authors.initials: CS
authors.lastname: Hau
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanda
authors.forename: Shinji
authors.initials: S
authors.lastname: Noda
authors.forename: Aya
authors.initials: A
authors.lastname: Tatsuta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamata
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Asano
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D054804:Cathelicidins / Q000096:biosynthesis*; D006801:Humans; D000077271:Imiquimod; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011565:Psoriasis / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023083:beta-Defensins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D023181:Antimicrobial Cationic Peptides; D022763:CCAAT-Enhancer-Binding Protein-alpha; D054804:Cathelicidins; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C506174:S100a7a protein, mouse; D050796:STAT3 Transcription Factor; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D054409:Nicotinamide Phosphoribosyltransferase; D011972:Receptor, Insulin; D048051:p38 Mitogen-Activated Protein Kinases; D000077271:Imiquimod