title: Interleukin-1alpha regulates antimicrobial peptide expression in human keratinocytes.
abstract: Human epidermis and epithelium serve as physiologic barriers to protect against noxious and infectious agents. Contributing to the defense against infection, epithelial cells express antimicrobial peptides (AMPs). The expression of AMPs in keratinocytes is generally regulated directly by bacteria and indirectly by proinflammatory cytokines. Bacteria may also regulate AMP expression by inducing keratinocyte expression of the autonomous proinflammatory cytokine, interleukin-1alpha (IL-1alpha). To test the hypothesis that AMP expression may be regulated by cell autonomous cytokines, we investigated the effect of IL-1alpha on the expression of AMPs in human keratinocytes (HaCaT cells) by microarray, northern blot, reverse transcriptase (RT)-PCR and western blot analyses. IL-1alpha increased expression of mRNA in a dose- and time-dependent manner specific for lipocalin 2, S100A8, S100A9 and secretory leukocyte protease inhibitor (SLPI) more than twofold relative to nonstimulated cells (control), and slightly upregulated S100A7 and beta-defensin-2. Furthermore, the expression of lipocalin 2, S100A7, S100A8, S100A9 and SLPI proteins were upregulated by IL-1alpha. On the other hand, HaCaT cells expressed mRNA specific for other AMPs, including cystatin 3, adrenomedullin, RNase-7 and mucin 5, which were unaffected by IL-1alpha treatment. These results suggest that the autonomous keratinocyte cytokine, IL-1alpha, selectively upregulates the expression of AMPs which may modulate innate epithelial cell immunity in skin and mucosa.
authors.affiliation: Department of Periodontology and Endodontology, Oral and Maxillofacial Dentistry, Division of Medico-Dental Dynamics and Reconstruction, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Bando
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kataoka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Mark C
authors.initials: MC
authors.lastname: Herzberg
authors.forename: Karen F
authors.initials: KF
authors.lastname: Ross
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nagata
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kido
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D053582:Interleukin-1alpha / Q000494:pharmacology / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D053582:Interleukin-1alpha