Inhibition of the production of rat cytokine-induced neutrophil chemoattractant (CINC)-1, a member of the interleukin-8 family, by adenovirus-mediated overexpression of I kappa B alpha

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 reactio ns 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 domai n 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 p roduction. For this purpose, we constructed two recombinant adenoviruses, A xCAI kappa B alpha and AxCAmutantI kappa B alpha, which express respectivel y 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 w ild and mutant I kappa B alpha by these adenovirus vectors inhibited NF-kap pa 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 s howed that the nondegradable mutant I kappa B alpha was approximately 30 ti mes more potent than the wild type in inhibiting CINC-1 production. These f indings demonstrate that CINC-1 production with NF-kappa B activation is pr imarily regulated by nonphosphorylated I kappa B alpha in the cytoplasm.