Abstract
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.
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Abbreviations
- AP:
-
activator protein
- E1A:
-
early region 1A
- GM-CSF:
-
granulocyte-macrophage colony-stimulating factor
- ICAM-1:
-
intercellular adhesion molecule-1
- NF:
-
nuclear factor
- RV:
-
rhinovirus
- TNF-α:
-
tumor necrosis factor-α
- VCAM:
-
vascular cell adhesion molecule
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Acknowledgements
The authors thank W.M. Lee for his gift of the pRV1611.1 infectious clone, S. White for providing 16HBE14o− cells, and A.R. Brasier and P.N. Cockerill for providing reporter plasmids.
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Supported by National Institutes of Health Grant HL56399.A.W.F. and J.A.K. contributed equally to the work.
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Funkhouser, A., Kang, JA., Tan, A. et al. Rhinovirus 16 3C Protease Induces Interleukin-8 and Granulocyte-Macrophage Colony-Stimulating Factor Expression in Human Bronchial Epithelial Cells. Pediatr Res 55, 13–18 (2004). https://doi.org/10.1203/01.PDR.0000099801.06360.AB
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DOI: https://doi.org/10.1203/01.PDR.0000099801.06360.AB
