期刊
JOURNAL OF BIOCHEMISTRY
卷 127, 期 3, 页码 511-516出版社
JAPANESE BIOCHEMICAL SOC
DOI: 10.1093/oxfordjournals.jbchem.a022634
关键词
CINC-1; GRO; I kappa B alpha; NF-kappa B; recombinant adenovirus
Cytokine-induced neutrophil chemoattractant (CINC)-1, a counterpart of the human growth-regulated gene product (GRO) of the interleukin-8 family, has been suggested to play critical roles as a mediator of inflammatory reactions with neutrophil infiltration in rats, NF-kappa B has been speculated to be involved in the production of CINC-1, since the NF-kappa B-binding domain is important for the CINC-1 promoter activity in several of our reporter assays, In the present study, we examined the effects of an overexpression of I kappa B alpha, a specific natural inhibitor of NF-kappa B, on CINC-1 production. For this purpose, we constructed two recombinant adenoviruses, AxCAI kappa B alpha and AxCAmutantI kappa B alpha, which express respectively wild I kappa B alpha and a mutated nondegradable I kappa B alpha in which serine residues 32 and 36 are replaced by alanine residues. Transfecting wild and mutant I kappa B alpha by these adenovirus vectors inhibited NF-kappa B activation and CINC-1 production, which were both caused by IL-1 beta stimulation in the normal rat kidney epithelial cell line NRK52E, We also showed that the nondegradable mutant I kappa B alpha was approximately 30 times more potent than the wild type in inhibiting CINC-1 production. These findings demonstrate that CINC-1 production with NF-kappa B activation is primarily regulated by nonphosphorylated I kappa B alpha in the cytoplasm.
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