Role of NF-kappa B in cytokine production induced from human airway epithelial cells by rhinovirus infection

• Published in: The Journal of immunology (1950) 2000-09, Vol.165 (6), p.3384-3392
• Main Authors: Kim, J, Sanders, S P, Siekierski, E S, Casolaro, V, Proud, D
• Format: Article
• Language: English
• Subjects: Bronchi - drug effects; Bronchi - immunology; Bronchi - metabolism; Bronchi - virology; Budesonide - pharmacology; Calpain - antagonists & inhibitors; Cell Line; Cytokines - biosynthesis; Cytokines - genetics; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - virology; Glycoproteins - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Human rhinovirus 16; Humans; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukin-6 - metabolism; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Interleukin-8 - metabolism; NF-kappa B - biosynthesis; NF-kappa B - metabolism; NF-kappa B - physiology; Nitric Oxide Donors - pharmacology; Promoter Regions, Genetic - immunology; Rhinovirus - drug effects; Rhinovirus - immunology; RNA, Messenger - biosynthesis; Sulfasalazine - pharmacology; Time Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.6.3384

Infection of human epithelial cells with human rhinovirus (HRV)-16 induces rapid production of several proinflammatory cytokines, including IL-8, IL-6, and GM-CSF. We evaluated the role of NF-kappaB in HRV-16-induced IL-8 and IL-6 production by EMSA using oligonucleotides corresponding to the binding sites for NF-kappaB in the IL-6 and IL-8 gene promoters. Consistent with the rapid induction of mRNA for IL-8 and IL-6, maximal NF-kappaB binding to both oligonucleotides was detected at 30 min after infection. NF-kappaB complexes contained p65 and p50, but not c-Rel. The IL-8 oligonucleotide bound recombinant p50 with only about one-tenth the efficiency of the IL-6 oligonucleotide, even though epithelial cells produced more IL-8 protein than IL-6. Neither the potent glucocorticoid, budesonide (10-7 M), nor a NO donor inhibited NF-kappaB binding to either cytokine promoter or induction of mRNA for either IL-8 or IL-6. Sulfasalazine and calpain inhibitor I, inhibitors of NF-kappaB activation, blocked HRV-16-induced formation of NF-kappaB complexes with oligonucleotides from both cytokines, but did not inhibit mRNA induction for either cytokine. By contrast, sulfasalazine clearly inhibited HRV-16 induction of mRNA for GM-CSF in the same cells. Thus, HRV-16 induces epithelial expression of IL-8 and IL-6 by an NF-kappaB-independent pathway, whereas induction of GM-CSF is at least partially dependent upon NF-kappaB activation.