Virus-induced secretion of pro-inflammatory chemokines (e.g. RANTES, IL-8) by airway epithelial cells helps to initiate anti-viral responses and airway inflammation by enhancing inflammatory cell recruitment. To define mechanisms for virus-induced chemokine secretion, monolayers of non-transformed bronchial epithelial cells were transfected or incubated with poly-IC (synthetic double-stranded [ds] RNA), rhinovirus dsRNA, or single-stranded RNA (ssRNA), and the secretion of selected chemokines was determined. Transfection or incubation with dsRNA, but not ssRNA, significantly enhanced secretion of RANTES and IL-8, but not eotaxin or MIP-1α. Mechanistically, dsRNA induced and activated PKR (double-stranded RNA-dependent protein kinase), and activated NF-κB and p38 MAP kinase. Furthermore, the PKR inhibitor 2-aminopurine significantly blocked dsRNA-induced RANTES and IL-8 secretion, while the p38 MAP kinase inhibitor SB203580 suppressed dsRNA-induced IL-8 but not RANTES. These findings indicate that dsRNA selectively induce the secretion of chemokines such as IL-8 and RANTES, and implicate dsRNA-sensitive signaling proteins in this process. Moreover, these data suggest that this may be an important mechanism for the selective secretion of chemokines by viruses (eg rhinovirus, RSV, influenza) that synthesize dsRNA during replication. 2 Abbreviations RV, rhinovirus; BE, bronchial epithelial; ds, double-stranded; ss, single-stranded; poly IC, polydeoxyinosinic-deoxycytidylic acid; PKR, double-stranded RNA-dependen
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