A GRANULOCYTE INHIBITORY PROTEIN OVEREXPRESSED IN CHRONIC RENAL-DISEASE REGULATES EXPRESSION OF INTERLEUKIN-6 AND INTERLEUKIN-8

Growing evidence suggests that cytokine expression is influenced by lo cally produced mediators, thus modifying the pluripotential effects of cytokines toward a tissue-specific inflammatory reaction. The granulo cyte inhibitory protein (GIP), a 23-kDa protein found to be significan tly overexpressed in patients with chronic renal failure, increases au tocrine transcription and expression of interleukin (IL) 6 and IL-8 in human mesangial cells. Moreover, GIP alone induced the transcription of c-jun mRNA; however, in combination with IL-6, it stimulated de nov o synthesis of DNA and the transcription of both c-jun and c-fos genes . The data suggest that the overall effect of GIP results in the modul ation of the glomerular response to injury and contributes to the prog ression of glomerulosclerosis.