title: Visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes.
abstract: Psoriasis patients are frequently associated with metabolic syndromes. Such associations are possibly mediated by adipokines. We investigated the in vitro effects of visfatin (an adipokine) on chemokine expression in human keratinocytes. Normal human keratinocytes were incubated with visfatin, and their chemokine production was analyzed by ELISA and RT-PCR. Visfatin enhanced TNF-α-induced CXC chemokine ligand (CXCL) 8, CXCL10, and CC chemokine ligand (CCL) 20 secretion and mRNA expression in keratinocytes, although visfatin alone was ineffective. A small interfering RNA against nuclear factor-κB (NF-κB) p65 suppressed the visfatin-induced production of CXCL8, CXCL10, and CCL20 whereas a small interfering RNA against signal transducer and activator of transcription (STAT) 3 suppressed CXCL8 induction. This indicates the involvement of NF-κB in CXCL8, CXCL10, and CCL20 induction by visfatin and the involvement of STAT3 in CXCL8 induction. Visfatin alone increased the transcriptional activity and tyrosine phosphorylation of STAT3, which was suppressed by Janus kinase (JAK) 2 inhibitor. Visfatin enhanced basal and TNF-α-induced NF-κB activity and inhibitory κB (IκB) α phosphorylation, which was suppressed by IκB kinase inhibitor. Visfatin induced the tyrosine and serine phosphorylation of JAK2 and IκB kinase α/β, respectively. Intraperitoneal injection of visfatin elevated mRNA and protein levels of CXCL1, CXCL10, and CCL20 in murine skin. These results suggest that visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes and homologous chemokine production in murine skin. Visfatin may induce the infiltration of type 1 or type 17 helper T cells or neutrophils to the skin via chemokine induction and thus link metabolic syndromes to psoriasis.
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-Ku, Tokyo 173-8605, Japan. nmk@med.teikyo-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Kanda
authors.forename: C S
authors.initials: CS
authors.lastname: Hau
authors.forename: Y
authors.initials: Y
authors.lastname: Tada
authors.forename: A
authors.initials: A
authors.lastname: Tatsuta
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000096:biosynthesis*; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis*; D053614:Janus Kinase 2 / Q000502:physiology; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000502:physiology; D009536:Niacinamide; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology*; D010430:Pentosyltransferases / Q000502:physiology; D011565:Psoriasis / Q000209:etiology; D011972:Receptor, Insulin / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C108355:CCL20 protein, human; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D016209:Interleukin-8; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D010430:Pentosyltransferases; D054409:Nicotinamide Phosphoribosyltransferase; D011972:Receptor, Insulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051550:I-kappa B Kinase; C021864:nicotinate phosphoribosyltransferase