title: Increased serum leucine, leucine-37 levels in psoriasis: positive and negative feedback loops of leucine, leucine-37 and pro- or anti-inflammatory cytokines.
abstract: Expression of leucine, leucine-37 (LL-37) is enhanced in keratinocytes of skin lesions with psoriasis. We examined serum LL-37 levels in patients with psoriasis vulgaris. Serum LL-37 levels in patients were higher than in normal controls, and were reduced after cyclosporine A treatment. In both groups, LL-37 and interleukin (IL)-17 levels inversely correlated. In patients, LL-37 levels correlated with interferon (IFN)-γ and IL-10 levels. In controls, LL-37 levels inversely correlated with tumor necrosis factor (TNF)-α, IL-6, IL-1β, and IL-22 levels. IFN-γ, IL-17, IL-22, TNF-α, IL-6, and IL-1β enhanced, and IL-10, IL-4, IL-13, and cyclosporine A suppressed, LL-37 secretion from keratinocytes and neutrophils. LL-37 enhanced IFN-γ, IL-4, IL-13, and TNF-α secretion from CD3/CD28-stimulated T cells, suppressed TNF-α, IL-1β, IL-6, and IL-10 secretion from lipopolysaccharide-stimulated monocytes, and IL-17, IL-22, IL-1β, IL-6, and IL-10 secretion from CD3/CD28-stimulated T cells. LL-37 may sustain its production by enhancing IFN-γ or reducing IL-10 production, while suppressing its production by reducing IL-17, IL-22, TNF-α, IL-1β, or IL-6 and enhancing IL-4 or IL-13 production. In patients, systemic LL-37 production is enhanced, and an IFN-γ/LL-37-positive feedback loop may exist. In controls, negative feedback by LL-37 on TNF-α, IL-1β, IL-22, and IL-6 may exist. In both groups, negative feedback by LL-37 on IL-17 may exist. LL-37 may act as an effector and regulator.
authors.affiliation: Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanda
authors.forename: Takeko
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamata
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000097:blood*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; D016753:Interleukin-10