Rhinovirus 16 3C Protease Induces Interleukin-8 and Granulocyte-Macrophage Colony-Stimulating Factor Expression in Human Bronchial Epithelial Cells

Rhinovirus (RV), a member of the Picornaviridae family, accounts for many virus-induced asthma exacerbations. RV induces airway cell chemokine expression both in vivo and in vitro . Because of the known interactions of proteases with cellular functions, we hypothesized that RV 3C protease is sufficient for cytokine up-regulation. A cDNA encoding RV16 3C protease was constructed by PCR amplification and transfected into 16HBE14o− human bronchial epithelial cells. 3C protease induced expression of both IL-8 and GM-CSF, as well as transcription from both the IL-8 and GM-CSF promoters. 3C expression also induced activator protein 1 and NF-κB transcriptional activation. Finally, mutation of IL-8 promoter AP-1 and NF-κB promoter sequences significantly reduced 3C-induced responses. Together, these data suggest expression of RV16 3C protease is sufficient to induce chemokine expression in human bronchial epithelial cells, and does so in an AP-1- and NF-κB–dependent manner.