title: Low concentrations of LL-37 alter IL-8 production by keratinocytes and bronchial epithelial cells in response to proinflammatory stimuli.
abstract: The immunomodulatory cationic host defence peptide LL-37 plays an important role in epithelial innate immunity; at higher concentrations (20-50 microg mL(-1)) associated with inflammation, LL-37 elicits the production of cytokines and chemokines. It was demonstrated here that lower, physiologically relevant LL-37 concentrations (2-3 microg mL(-1)) altered epithelial cell responses to proinflammatory stimuli. In combination with interleukin-1beta (IL-1beta) and the Toll-like receptor-5 (TLR5) agonist flagellin, these low concentrations of LL-37 synergistically increased IL-8 production by both proliferating and differentiated keratinocytes and by bronchial epithelial cells. In combination with the TLR2/1 agonist PAM3CSK4, LL-37 synergistically induced transcription and the release of both IL-8 and IL-6 from primary bronchial epithelial cells; the IL-8 response was demonstrated to be regulated by epidermal growth factor receptor signalling. Treatment of bronchial epithelial cells with LL-37 and the TLR3 agonist polyI:C resulted in synergistic increases in IL-8 release and cytotoxicity. These data indicate that low concentrations of LL-37 may alter epithelial responses to infecting microorganisms in vivo.
authors.affiliation: Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Lower Mall Research Station, Vancouver, BC, Canada V6T 1Z4.
authors.forename: Niall C J
authors.initials: NC
authors.lastname: Filewod
authors.forename: Jelena
authors.initials: J
authors.lastname: Pistolic
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology*; D005408:Flagellin / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000276:immunology*; D055666:Lipopeptides / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D005408:Flagellin; D011070:Poly I-C; D054804:Cathelicidins