Inhibition of the Production of Rat Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, a Member of the Interleukin-8 Family, by Adenovirus-Mediated Overexpression of IκBα

抄録

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-kB has been speculated to be involved in the production of CINC-1, since the NF-kB-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 IkBα, a specific natural inhibitor of NF-kB, on CINC-1 production. For this purpose, we constructed two recombinant adenoviruses, AxCAIkBα and AxCAmutantIkBα, which express respectively wild IkBα and a mutated nondegradable IkBα in which serine residues 32 and 36 are replaced by alanine residues. Transfecting wild and mutant IkBα by these adenovirus vectors inhibited NF-kB activation and CINC-1 production, which were both caused by IL-1β stimulation in the normal rat kidney epithelial cell line NRK-52E. We also showed that the nondegradable mutant IkBα was approximately 30 times more potent than the wild type in inhibiting CINC-1 production. These findings demonstrate that CINC-1 production with NF-kB activation is primarily regulated by nonphosphorylated IkBα in the cytoplasm.