title: Streptococcus pyogenes induces epithelial inflammatory responses through NF-kappaB/MAPK signaling pathways.
abstract: Innate immunity involves a cascade of inflammatory events, resulting in the secretion of chemokines and cytokines to recruit mediator cells in adaptive immunity. To study epithelial inflammatory responses initiated by Streptococcus pyogenes infection, we investigated chemotaxis ability in the supernatant of infected human respiratory epithelial HEp-2 cells. Our results showed that these supernatants showed significantly increased ability to attract monocytes, implying the release of inflammatory chemoattractants into the medium. Expression of interleukin (IL)-8 and IL-6 in HEp-2 cells was significantly increased at both the mRNA and protein levels after infection with S. pyogenes. Electrophoretic mobility shift and reporter-gene assays demonstrated that the transcription factors NF-kappaB and AP-1, regulated by mitogen-activated protein (MAP) kinase, were activated after streptococcal infection. The increases in mRNAs for IL-8 and IL-6 were abrogated by addition of NF-kappaB and MAP kinase inhibitors, suggesting that the upregulation of IL-8 and IL-6 is mediated through NF-kappaB and MAP kinase signaling pathways. Taken together, our results indicate that S. pyogenes infection of epithelial cells induces the secretion of pro-inflammatory chemokines/cytokines through activation of NF-kappaB and MAP kinase signaling pathways. These early innate responses initiated by S. pyogenes-infected respiratory epithelial cells may recruit immune cells to the airway and induce inflammation.
authors.affiliation: Graduate Institutes of Medical Biotechnology, Department of Laboratory Medicine and Biotechnology, Medical College, Tzu-Chi University, 701, Chung Yan Road Section 3, Hualien 970, Taiwan. pjtsai@mail.tcu.edu.tw
authors.forename: Pei-Jane
authors.initials: PJ
authors.lastname: Tsai
authors.forename: Ying-Huei
authors.initials: YH
authors.lastname: Chen
authors.forename: Chieh-Hsing
authors.initials: CH
authors.lastname: Hsueh
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Hsieh
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Tsou
mesh_terms: D047310:Apigenin / Q000494:pharmacology; D001323:Autoantibodies / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000201:enzymology / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism; D020298:U937 Cells
chemical_list: D001323:Autoantibodies; D007093:Imidazoles; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018808:Transcription Factor AP-1; D047310:Apigenin; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580