title: Triggering of TLR3 by polyI:C in human corneal epithelial cells to induce inflammatory cytokines.
abstract: Epithelial cells of the ocular surface are key in the first-line defense as a part of the mucosal immune system against pathogens. We investigated whether polyI:C induces the production by human corneal epithelial cells (HCEC) of pro-inflammatory cytokines and IFN-beta, and whether Toll-like receptor (TLR)-3 expression is amplified by polyI:C. TLR3 was expressed on the surface of HCEC. Stimulation with polyI:C elicited the elevated production and mRNA expression of IL-6 and IL-8 in HCEC. While polyI:C induced IFN-beta, far stronger than human fibroblasts, and TLR3 gene expression in HCEC, LPS stimulation did not. Similarly, polyI:C, but not LPS, induced the gene expression of IkappaBalpha and MAIL, members of the IkappaB family, in HCEC. The innate immune response of HCEC is distinct from that of immune-competent cells, and we suggest that this is indicative of the symbiotic relationship between corneal epithelium and microbes inhabiting the ocular surface.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. mueta@ophth.kpu-m.ac.jp
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueta
authors.forename: Junji
authors.initials: J
authors.lastname: Hamuro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D019573:Epithelium, Corneal / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D009687:Nuclear Proteins / Q000096:biosynthesis; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C000606204:NFKBIA protein, human; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D000072000:NF-KappaB Inhibitor alpha; D016899:Interferon-beta; D011070:Poly I-C