Role of NF-kappa B in cytokine production induced from human airway epithelial cells by rhinovirus infection.
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.
Kim
J
J
Divisions of Clinical Immunology, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Sanders
S P
SP
Siekierski
E S
ES
Casolaro
V
V
Proud
D
D
D001980:Bronchi / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D019819:Budesonide / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D006023:Glycoproteins / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D012229:Rhinovirus / Q000187:drug effects / Q000276:immunology*; D012460:Sulfasalazine / Q000494:pharmacology; D013997:Time Factors
D016207:Cytokines; D006023:Glycoproteins; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; C039304:calpain inhibitors; D012460:Sulfasalazine; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002154:Calpain