title: Innate immune response to H3N2 and H1N1 influenza virus infection in a human lung organ culture model.
abstract: We studied cytokine responses to influenza virus PR8 (H1N1) and Oklahoma/309/06 (OK/06, H3N2) in a novel human lung tissue model. Exposure of the model to influenza virus rapidly activated the mitogen-activated protein kinase signaling (MAPK) pathways ERK, p38 and JNK. In addition, RNase protection assay demonstrated the induction of several cytokine and chemokine mRNAs by virus. This finding was reflected at the translational level as IL-6, MCP-1, MIP-1 alpha/beta, IL-8 and IP-10 proteins were induced as determined by ELISA. Immunohistochemistry for IP-10 and MIP-1 alpha revealed that alveolar epithelial cells and macrophages were the source of these two cytokines. Taken together, both PR8 and OK/06 cause similar induction of cytokines in human lung, although OK/06 is less effective at inducing the chemokines MCP-1 and IL-8. This human organ culture model should thus provide a relevant platform to study the biological responses of human lung to influenza virus infection.
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, RM 425, RP1, 800 N. Research Pkwy., Oklahoma City, OK 73104, USA. wenxin-wu@ouhsc.edu
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wu
authors.forename: J Leland
authors.initials: JL
authors.lastname: Booth
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Duggan
authors.forename: Shuhua
authors.initials: S
authors.lastname: Wu
authors.forename: Krupa B
authors.initials: KB
authors.lastname: Patel
authors.forename: K Mark
authors.initials: KM
authors.lastname: Coggeshall
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Metcalf
mesh_terms: D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004790:Enzyme Induction / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000502:physiology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008168:Lung / Q000276:immunology / Q000821:virology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D020929:Mitogen-Activated Protein Kinase Kinases