title: MxA expression induced by α-defensin in healthy human periodontal tissue.
abstract: Although periodontal tissue is continually challenged by microbial plaque, it is generally maintained in a healthy state. To understand the basis for this, we investigated innate antiviral immunity in human periodontal tissue. The expression of mRNA encoding different antiviral proteins, myxovirus resistance A (MxA), protein kinase R (PKR), oligoadenylate synthetase (OAS), and secretory leukocyte protease inhibitor (SLPI) were detected in both healthy tissue and that with periodontitis. Immunostaining data consistently showed higher MxA protein expression in the epithelial layer of healthy gingiva as compared with tissue with periodontitis. Human MxA is thought to be induced by type I and III interferons (IFNs) but neither cytokine type was detected in healthy periodontal tissues. Treatment in vitro of primary human gingival epithelial cells (HGECs) with α-defensins, but not with the antimicrobial peptides β-defensins or LL-37, led to MxA protein expression. α-defensin was also detected in healthy periodontal tissue. In addition, MxA in α-defensin-treated HGECs was associated with protection against avian influenza H5N1 infection and silencing of the MxA gene using MxA-targeted-siRNA abolished this antiviral activity. To our knowledge, this is the first study to uncover a novel pathway of human MxA induction, which is initiated by an endogenous antimicrobial peptide, namely α-defensin. This pathway may play an important role in the first line of antiviral defense in periodontal tissue.
authors.affiliation: Department of Periodontology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. rangsini.m@chula.ac.th
authors.forename: Rangsini
authors.initials: R
authors.lastname: Mahanonda
authors.forename: Noppadol
authors.initials: N
authors.lastname: Sa-Ard-Iam
authors.forename: Pimprapa
authors.initials: P
authors.lastname: Rerkyen
authors.forename: Arunee
authors.initials: A
authors.lastname: Thitithanyanont
authors.forename: Keskanya
authors.initials: K
authors.lastname: Subbalekha
authors.forename: Sathit
authors.initials: S
authors.lastname: Pichyangkul
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D005881:Gingiva / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology / Q000378:metabolism; D007251:Influenza, Human / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000276:immunology / Q000378:metabolism; D023084:alpha-Defensins / Q000276:immunology* / Q000378:metabolism; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D023084:alpha-Defensins; D023083:beta-Defensins; C054566:protein kinase P; D017346:Protein Serine-Threonine Kinases; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins; D054804:Cathelicidins