title: Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands.
abstract: Here we show that keratinocytes in psoriatic lesional skin express increased Toll-like receptor (TLR) 9 that similarly localizes with elevated expression of the cathelicidin antimicrobial peptide LL-37. In culture, normal human keratinocytes exposed to LL-37 increased TLR9 expression. Furthermore, when keratinocytes were exposed to LL-37 and subsequently treated with TLR9 ligands, such as CpG or genomic DNA, they greatly increased production of type I IFNs. This response mimicked observations in the epidermis of psoriatic lesional skin as keratinocytes in psoriatic lesions produce greater amounts of IFN-β than normal skin lacking LL-37. The mechanism for induction of type I IFNs in keratinocytes was dependent on TLR9 expression but not on a DNA-LL-37 complex. These findings suggest that keratinocytes recognize and respond to DNA and can actively participate in contributing to the immunological environment that characterizes psoriasis.
authors.affiliation: Division of Dermatology, Department of Medicine, University of California, San Diego and VA San Diego Healthcare System, San Diego, California, USA. zanemori@cc.okayama-u.ac.jp
authors.forename: Shin
authors.initials: S
authors.lastname: Morizane
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Beda
authors.initials: B
authors.lastname: Mühleisen
authors.forename: Paul F
authors.initials: PF
authors.lastname: Kotol
authors.forename: Masamoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Yumi
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
authors.forename: Tissa
authors.initials: T
authors.lastname: Hata
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D023181:Antimicrobial Cationic Peptides; D001706:Biopsy; D054804:Cathelicidins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000276:immunology / Q000494:pharmacology; D000078404:Epidermal Cells; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008024:Ligands; D011565:Psoriasis / Q000276:immunology* / Q000503:physiopathology*; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D007370:Interferon Type I; D008024:Ligands; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D016899:Interferon-beta; D004247:DNA