RRC ID 71653
Author Mori N, Oishi K, Sar B, Mukaida N, Nagatake T, Matsushima K, Yamamoto N.
Title Essential role of transcription factor nuclear factor-kappaB in regulation of interleukin-8 gene expression by nitrite reductase from Pseudomonas aeruginosa in respiratory epithelial cells.
Journal Infect Immun
Abstract Persistent infection with Pseudomonas aeruginosa increases interleukin-8 (IL-8) levels and causes dense neutrophil infiltrations in the airways of patients with chronic airway diseases. Recently, we have reported that nitrite reductase from P. aeruginosa induces the production of IL-8 in respiratory cells, including bronchial epithelial cells. To determine the molecular mechanism(s) of nitrite reductase-induced IL-8 expression in respiratory cells, A549 epithelial cells were transfected with plasmids containing serial deletions of the 5'-flanking region of the IL-8 gene and then exposed to nitrite reductase. Nitrite reductase significantly enhanced IL-8 gene promoter-driven reporter activity. This increased IL-8 gene expression was inhibited by mutating the nuclear factor-kappaB (NF-kappaB) binding element. Nitrite reductase enhanced nuclear localization of the NF-kappaB binding complex. Furthermore, nitrite reductase induced the degradation of IkappaBalpha, the major cytoplasmic inhibitor of NF-kappaB, and the expression of IkappaBalpha mRNA. These data support the critical role of the activation of NF-kappaB in nitrite reductase-induced IL-8 gene expression in airway epithelium.
Volume 67(8)
Pages 3872-8
Published 1999-8-1
DOI 10.1128/IAI.67.8.3872-3878.1999
PMID 10417151
PMC PMC96667
MeSH DNA-Binding Proteins / metabolism Epithelial Cells / metabolism Gene Expression Regulation / drug effects* Humans I-kappa B Proteins* Interleukin-8 / genetics* Lung / metabolism* NF-KappaB Inhibitor alpha NF-kappa B / physiology* Nitrite Reductases / pharmacology* Promoter Regions, Genetic Pseudomonas aeruginosa / enzymology* Transcription Factor AP-1 / physiology Tumor Cells, Cultured
IF 3.201
Human and Animal Cells A549(RCB0098)