Interferon- Enhances Rhinovirus-Induced RANTES Secretion by Airway Epithelial Cells

Respiratory viruses, including rhinoviruses, infect respiratory epithelium and induce a variety of cytokines and chemokines that can initiate an inflammatory response. Cytokines, such as interferon (IFN)and tumor necrosis factor (TNF), could enhance epithelial cell activation by inducing virus receptors. To test this hypothesis, effects of IFNor TNFon expression of intercellular adhesion molecule (ICAM)-1, rhinovirus binding, and virus-induced chemokine secretion on A549 and human bronchial epithelial cells (HBEC) were determined. The results varied with the type of cell. IFNwas a stronger inducer of ICAM-1 and viral binding on HBEC, whereas TNFhad greater effects on A549 cells. In addition, IFN, but not TNF, synergistically enhanced regulated on activation, normal T cells expressed and secreted (RANTES) mRNA expression and protein secretion induced by RV16 or RV49. To determine whether IFNcould enhance RANTES secretion independent of effects on ICAM-1 and RV binding, HBEC were transfected with RV16 RNA in the presence or absence of IFN. RV16 RNA alone stimulated RANTES secretion, and this effect was enhanced by IFN. These results demonstrate that IFNcan enhance rhinovirus-induced RANTES secretion by increasing viral binding, and through a second receptor-independent pathway. These findings suggest that IFN, by upregulating RANTES secretion, could be an important regulator of the initial immune response to rhinovirus infections.