title: Antiviral immune responses in H5N1-infected human lung tissue and possible mechanisms underlying the hyperproduction of interferon-inducible protein IP-10.
abstract: Information on the immune response against H5N1 within the lung is lacking. Here we describe the sustained antiviral immune responses, as indicated by the expression of MxA protein and IFN-alpha mRNA, in autopsy lung tissue from an H5N1-infected patient. H5N1 infection of primary bronchial/tracheal epithelial cells and lung microvascular endothelial cells induced IP-10, and also up-regulated the retinoic acid-inducible gene-I (RIG-I). Down-regulation of RIG-I gene expression decreased IP-10 response. Co-culturing of H5N1-infected pulmonary cells with TNF-alpha led to synergistically enhanced production of IP-10. In the absence of viral infection, TNF-alpha and IFN-alpha also synergistically enhanced IP-10 response. Methylprednisolone showed only a partial inhibitory effect on this chemokine response. Our findings strongly suggest that both the H5N1 virus and the locally produced antiviral cytokines; IFN-alpha and TNF-alpha may have an important role in inducing IP-10 hyperresponse, leading to inflammatory damage in infected lung.
authors.affiliation: Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Arunee
authors.initials: A
authors.lastname: Thitithanyanont
authors.forename: Anneke
authors.initials: A
authors.lastname: Engering
authors.forename: Monkol
authors.initials: M
authors.lastname: Uiprasertkul
authors.forename: Peeraya
authors.initials: P
authors.lastname: Ekchariyawat
authors.forename: Suwimon
authors.initials: S
authors.lastname: Wiboon-Ut
authors.forename: Romchat
authors.initials: R
authors.lastname: Kraivong
authors.forename: Amporn
authors.initials: A
authors.lastname: Limsalakpetch
authors.forename: Utaiwan
authors.initials: U
authors.lastname: Kum-Arb
authors.forename: Kosol
authors.initials: K
authors.lastname: Yongvanitchit
authors.forename: Noppadol
authors.initials: N
authors.lastname: Sa-Ard-Iam
authors.forename: Pimprapa
authors.initials: P
authors.lastname: Rukyen
authors.forename: Rangsini
authors.initials: R
authors.lastname: Mahanonda
authors.forename: Kamon
authors.initials: K
authors.lastname: Kawkitinarong
authors.forename: Prasert
authors.initials: P
authors.lastname: Auewarakul
authors.forename: Pongsak
authors.initials: P
authors.lastname: Utaisincharoen
authors.forename: Stitaya
authors.initials: S
authors.lastname: Sirisinha
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Mason
authors.forename: Mark M
authors.initials: MM
authors.lastname: Fukuda
authors.forename: Sathit
authors.initials: S
authors.lastname: Pichyangkul
mesh_terms: D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007251:Influenza, Human / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000821:virology*; D008775:Methylprednisolone / Q000494:pharmacology; D064547:Myxovirus Resistance Proteins; D011024:Pneumonia, Viral / Q000276:immunology*; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C452820:RIGI protein, human; D019204:GTP-Binding Proteins; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D008775:Methylprednisolone