Respiratory syncytial virus infection activates STAT signaling in human epithelial cells
Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected...
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| Published in: | Biochemical and biophysical research communications Vol. 306; no. 2; pp. 616 - 622 |
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| Main Authors: | , , , , , , , , |
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Elsevier Inc
27-06-2003
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| Abstract | Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected human alveolar type II (A549) epithelial cells identified several genes whose expression was altered from −5.5 to +56.4-fold. Four of the highly expressed genes contained STAT-binding elements. In A549 and normal human bronchial epithelial cells (NHBE), RSV induced phosphorylation and nuclear translocation of STAT-1α that was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor or transfection with dominant-negative STAT-1α blocked STAT-1α activation and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked this activation. Thus, activation of the STAT-1α and STAT-3 pathways play a role in RSV infection. |
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| AbstractList | Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected human alveolar type II (A549) epithelial cells identified several genes whose expression was altered from -5.5 to +56.4-fold. Four of the highly expressed genes contained STAT-binding elements. In A549 and normal human bronchial epithelial cells (NHBE), RSV induced phosphorylation and nuclear translocation of STAT-1alpha that was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor or transfection with dominant-negative STAT-1alpha blocked STAT-1alpha activation and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked this activation. Thus, activation of the STAT-1alpha and STAT-3 pathways play a role in RSV infection. Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected human alveolar type II (A549) epithelial cells identified several genes whose expression was altered from -5.5 to +56.4-fold. Four of the highly expressed genes contained STAT-binding elements. In A549 and normal human bronchial epithelial cells (NHBE), RSV induced phosphorylation and nuclear translocation of STAT-1 alpha that was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor or transfection with dominant-negative STAT-1 alpha blocked STAT-1 alpha activation and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked this activation. Thus, activation of the STAT-1 alpha and STAT-3 pathways play a role in RSV infection. Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected human alveolar type II (A549) epithelial cells identified several genes whose expression was altered from −5.5 to +56.4-fold. Four of the highly expressed genes contained STAT-binding elements. In A549 and normal human bronchial epithelial cells (NHBE), RSV induced phosphorylation and nuclear translocation of STAT-1α that was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor or transfection with dominant-negative STAT-1α blocked STAT-1α activation and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked this activation. Thus, activation of the STAT-1α and STAT-3 pathways play a role in RSV infection. |
| Author | Mane, Srikant Hellermann, Gary R San Juan, Homero Behera, Aruna K Mohapatra, Alexander Kong, Xiaoyuan Mohapatra, Shyam S Kumar, Mukesh Lockey, Richard F |
| Author_xml | – sequence: 1 givenname: Xiaoyuan surname: Kong fullname: Kong, Xiaoyuan organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA – sequence: 2 givenname: Homero surname: San Juan fullname: San Juan, Homero organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA – sequence: 3 givenname: Mukesh surname: Kumar fullname: Kumar, Mukesh organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA – sequence: 4 givenname: Aruna K surname: Behera fullname: Behera, Aruna K organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA – sequence: 5 givenname: Alexander surname: Mohapatra fullname: Mohapatra, Alexander organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA – sequence: 6 givenname: Gary R surname: Hellermann fullname: Hellermann, Gary R organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA – sequence: 7 givenname: Srikant surname: Mane fullname: Mane, Srikant organization: Functional Genomics Core, H. Lee Moffitt Cancer Center, University of South Florida College of Medicine and VA Hospital, Tampa, FL, USA – sequence: 8 givenname: Richard F surname: Lockey fullname: Lockey, Richard F organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA – sequence: 9 givenname: Shyam S surname: Mohapatra fullname: Mohapatra, Shyam S email: smohapat@hsc.usf.edu organization: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, MDC-19, Rm 2536, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12804610$$D View this record in MEDLINE/PubMed |
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| Keywords | Signal transduction STAT Transcription factors Respiratory syncytial virus Microarray Gene expression |
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| Snippet | Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood.... |
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| SubjectTerms | Active Transport, Cell Nucleus Cell Line DNA - metabolism Electrophoresis, Polyacrylamide Gel Epithelial Cells - metabolism Gene expression Genes, Reporter Heparin - metabolism Heparin Lyase - metabolism Humans Immunoblotting Immunohistochemistry Interferon-Stimulated Gene Factor 3 Interleukin-6 - metabolism Microarray Microscopy, Fluorescence Models, Genetic Oligonucleotide Array Sequence Analysis Phosphorylation Promoter Regions, Genetic Respiratory syncytial virus Respiratory Syncytial Virus Infections - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Signal Transduction STAT Transcription factors Transcription Factors - metabolism Transcription, Genetic Transfection Tumor Cells, Cultured |
| Title | Respiratory syncytial virus infection activates STAT signaling in human epithelial cells |
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