title: Host defense (Antimicrobial) peptide, human β-defensin-3, improves the function of the epithelial tight-junction barrier in human keratinocytes.
abstract: Human β-defensins (hBDs) are host defense peptides that not only exhibit microbicidal properties but also stimulate various cellular activities, including keratinocyte proliferation, migration, and wound healing. hBDs are overexpressed in the skin in cases of psoriasis but are downregulated in atopic dermatitis skin, although both diseases are associated with stratum corneum barrier defects. Because the tight-junction (TJ) barrier is also dysfunctional in both atopic dermatitis and psoriasis patients, we hypothesized that hBDs may regulate the TJ barrier function in keratinocytes. We observed that, among the hBDs tested, only hBD-3 increased the expression of several claudins and their localization along the cell-cell borders. In addition, hBD-3 elevated the transepithelial electrical resistance and reduced the paracellular permeability of keratinocyte layers, and this effect was reversed by the claudin inhibitor ochratoxin A, CCR6 antibody, and CCR6 small interfering RNA. Moreover, hBD-3 enhanced the activation of Rac1, atypical protein kinase C, glycogen synthase kinase-3, and phosphatidylinositol 3 kinase, which are required for the hBD-3-mediated regulation of the TJ barrier function, as evidenced by the effects of their respective inhibitors. Collectively, our findings provide evidence regarding the contribution of host defense peptides to the innate immunity of skin by regulating TJ barrier function, in addition to their antimicrobial and other immunomodulatory activities.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Chanisa
authors.initials: C
authors.lastname: Kiatsurayanon
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: francois@juntendo.ac.jp.
authors.forename: François
authors.initials: F
authors.lastname: Niyonsaba
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Rithee
authors.initials: R
authors.lastname: Smithrithee
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ushio
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hara
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D002478:Cells, Cultured; D017097:Electric Impedance; D004848:Epithelium / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D015603:Keratinocytes / Q000502:physiology*; D009793:Ochratoxins / Q000494:pharmacology; D010539:Permeability; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D054399:Receptors, CCR6 / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology*; D023083:beta-Defensins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology
chemical_list: C106311:CCR6 protein, human; C422950:DEFB103A protein, human; D009793:Ochratoxins; D054399:Receptors, CCR6; D023083:beta-Defensins; C025589:ochratoxin A; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3; D020830:rac1 GTP-Binding Protein