TY - JOUR
T1 - Role of NF-κB in cytokine production induced from human airway epithelial cells by rhinovirus infection
AU - Kim, J.
AU - Sanders, S. P.
AU - Siekierski, E. S.
AU - Casolaro, V.
AU - Proud, D.
PY - 2000/9/15
Y1 - 2000/9/15
N2 - 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-κB in HRV-16-induced IL-8 and IL-6 production by EMSA using oligonucleotides corresponding to the binding sites for NF-κB in the IL-6 and IL-8 gene promoters. Consistent with the rapid induction of mRNA for IL-8 and IL-6, maximal NF-κB binding to both oligonucleotides was detected at 30 min after infection. NF-κB 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-κB binding to either cytokine promoter or induction of mRNA for either IL-8 or IL-6. Sulfasalazine and calpain inhibitor I, inhibitors of NF-κB activation, blocked HRV-16-induced formation of NF-κB 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-κB-independent pathway, whereas induction of GM-CSF is at least partially dependent upon NF-κB activation.
AB - 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-κB in HRV-16-induced IL-8 and IL-6 production by EMSA using oligonucleotides corresponding to the binding sites for NF-κB in the IL-6 and IL-8 gene promoters. Consistent with the rapid induction of mRNA for IL-8 and IL-6, maximal NF-κB binding to both oligonucleotides was detected at 30 min after infection. NF-κB 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-κB binding to either cytokine promoter or induction of mRNA for either IL-8 or IL-6. Sulfasalazine and calpain inhibitor I, inhibitors of NF-κB activation, blocked HRV-16-induced formation of NF-κB 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-κB-independent pathway, whereas induction of GM-CSF is at least partially dependent upon NF-κB activation.
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U2 - 10.4049/jimmunol.165.6.3384
DO - 10.4049/jimmunol.165.6.3384
M3 - Article
C2 - 10975857
AN - SCOPUS:0034665299
SN - 0022-1767
VL - 165
SP - 3384
EP - 3392
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -