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To test this hypothesis in a cellular system, we examined the combined effects of RV39 and TNF-\u03b1, a cytokine increased in asthma and chronic obstructive pulmonary disease, on airway epithelial cell proinflammatory gene expression. Costimulation of 16HBE14o- human bronchial epithelial cells and primary mucociliary-differentiated tracheal epithelial cells with RV and TNF-\u03b1 induced synergistic increases in IL-8 and epithelial neutrophil attractant-78 production. Similar synergism was observed for IL-8 promoter activity, demonstrating that the effect is transcriptionally mediated. Whereas increases in ICAM-1 expression and viral load were noted 16\u201324 h after costimulation, cooperative effects between RV39 and TNF-\u03b1 were evident 4 h after stimulation and maintained despite incubation with blocking antibody to ICAM-1 given 2 h postinfection or UV irradiation of virus, implying that effects were not solely due to changes in ICAM-1 expression. Furthermore, RV39 infection induced phosphorylation of ERK and transactivation of the IL-8 promoter AP-1 site, which functions as a basal level enhancer, leading to enhanced TNF-\u03b1 responses. We conclude that RV infection and TNF-\u03b1 stimulation induce cooperative increases in epithelial cell chemokine expression, providing a cellular mechanism for RV-induced exacerbations of airways disease.<\/jats:p>","DOI":"10.1152\/ajplung.00060.2007","type":"journal-article","created":{"date-parts":[[2007,7,14]],"date-time":"2007-07-14T00:49:13Z","timestamp":1184374153000},"page":"L1021-L1028","source":"Crossref","is-referenced-by-count":25,"title":["Cooperative effects of rhinovirus and TNF-\u03b1 on airway epithelial cell chemokine expression"],"prefix":"10.1152","volume":"293","author":[{"given":"Dawn C.","family":"Newcomb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umadevi S.","family":"Sajjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti R.","family":"Nagarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Goldsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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