The Mxil proteins are biochemical and biological antagonists of c-myc oncoprotein. It has been reported that the overexpression pattern of c-myc might be similar to a molecular feature of early and late stages of human autosomal dominant polycystic kidney disease. We identified the cyst phenotype in Mxil-deficient mice aged 6-12 months using H&E staining. Some chemokines containing a protein domain similar to human IL-8, which is associated with the inflammatory response, were subsequently selected from the up-regulated genes. We confirmed the expression level of these chemokines and measured protein concentrations of IL-8 using ELISA in the Mxil-knockdown cells. IL-8 was found to be significantly increased in Mxil-knockdown cells. We found that p38 MAP kinase activation was involved in the signal transduction of the Mxil-inactivated secretion of IL-8. Therefore, we could suggest that the inactivation of Mxil leads to the inflammatory response and has the potential to induce polycystic renal disease. (c) 2007 Elsevier Inc. All rights reserved.