Streptococcus pyogenes induces epithelial inflammatory responses through NF-kappaB/MAPK signaling pathways.
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.
Tsai
Pei-Jane
PJ
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
Chen
Ying-Huei
YH
Hsueh
Chieh-Hsing
CH
Hsieh
Hsiao-Chun
HC
Liu
Ya-Hui
YH
Wu
Jiunn-Jong
JJ
Tsou
Chih-Cheng
CC
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
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