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IL-17A synergistically enhanced HRV-16-induced epithelial production of the neutrophil chemoattractant, IL-8, as well as human \u03b2-defensin-2 (HBD-2), a chemoattractant for immature dendritic cells and memory T cells, but suppressed viral production of the eosinophil chemoattractant, RANTES. These effects were not due to alterations of viral uptake or replication by IL-17A. The synergy between HRV-16 and IL-17A for IL-8 protein production was both dose- and time-dependent. IL-8 induction by IL-17A or HRV-16, alone and in combination, was reduced by inhibitors of the p38 and p44\/42 MAPK pathways. By contrast, induction of HBD-2 depended on the activation of the p38 and JNK pathways. The ability of IL-17A to synergistically enhance HRV-induced IL-8 is mediated posttranscriptionally, since IL-8 promoter activation by the combination of the two stimuli was merely additive, whereas the combination of IL-17A and HRV-16 led to stabilization of IL-8 mRNA. Similarly, stimulation of HBD-2 promoter constructs by the combination of IL-17A and HRV-16 was no more than the sum of the individual responses. Further studies are needed to examine HBD-2 mRNA stability. Taken together, these data represent the first demonstration that IL-17A can modify epithelial responses to HRV in a manner that would be expected to favor the recruitment of neutrophils, immature dendritic cells, and memory T cells to the airways.<\/jats:p>","DOI":"10.1152\/ajplung.00066.2007","type":"journal-article","created":{"date-parts":[[2007,6,2]],"date-time":"2007-06-02T01:18:27Z","timestamp":1180747107000},"page":"L505-L515","source":"Crossref","is-referenced-by-count":100,"title":["Interleukin-17A modulates human airway epithelial responses to human rhinovirus 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