title: Lipocalin-2 exacerbates psoriasiform skin inflammation by augmenting T-helper 17 response.
abstract: Lipocalin-2 (LCN2) is an antimicrobial protein and adipokine associated with insulin resistance, obesity and atherosclerotic disease. Psoriasis is a T-helper (Th)1/Th17-mediated, chronic inflammatory dermatosis related to metabolic syndromes and serum LCN2 levels are elevated in psoriatic patients. We examined the in vivo effects of LCN2 on topical imiquimod (IMQ)-induced psoriasiform skin in BALB/c mice and in vitro on human keratinocytes (KC). Clinically, i.p. injected LCN2 exacerbated erythema and scaling in IMQ-treated murine skin compared with phosphate-buffered saline injection alone, and it augmented interleukin (IL)-17A, IL-17F, IL-22, IL-23p19, IL-12p40, CCL20, tumor necrosis factor-α, chemokine (C-X-C motif) ligand (CXCL)1, CXCL2, DEFB4, DEFB14, LCN2 and S100A7 mRNA levels of IMQ-treated murine skin while it did not increase the mRNA levels of interferon-γ, IL-12p35 or CXCL10. LCN2 in synergy with IL-17 increased mRNA levels of CCL20, LCN2 and DEFB4A but not of CXCL10 in human KC in vitro. These results suggest that LCN2 enhances the expression of Th17 cytokines/chemokines and antimicrobial peptides in murine IMQ-treated psoriatic skin and KC. LCN2 may potentiate the development of psoriasis via the enhancement of Th17- and antimicrobial peptide-mediated inflammation.
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Carren S
authors.initials: CS
authors.lastname: Hau
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanda
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.|Department of Dermatology, University of Tokyo Faculty of Medicine, Tokyo, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Dermatology, University of Tokyo Faculty of Medicine, Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
authors.affiliation: Department of Dermatology, University of Tokyo Faculty of Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000378:metabolism; D005260:Female; D006801:Humans; D000077271:Imiquimod; D015603:Keratinocytes / Q000378:metabolism; D000071068:Lipocalin-2 / Q000502:physiology*; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000209:etiology* / Q000473:pathology; D012867:Skin / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*; D023083:beta-Defensins / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D023181:Antimicrobial Cationic Peptides; C108355:CCL20 protein, human; D054418:Chemokine CCL20; C106641:DEFB4A protein, human; D000071068:Lipocalin-2; D023083:beta-Defensins; D000077271:Imiquimod
keywords: T-helper 17 cytokines/chemokines; lipocalin-2; psoriasis