Factors produced by activated leukocytes alter renal epithelial cell differentiation

The development of tubulointerstitial fibrosis in inflammatory renal diseas es has been linked to disease progression to end-stage renal failure. Under standing the interactions of the factors influencing inflammation and activ ating the fibrotic process, that is, the inflammatory infiltrate and the re sident proximal tubular cells, may lead to a determination of the mechanism s that regulate tubulointerstitial fibrosis. We used an in vitro model of h uman proximal tubule cells that were stimulated with supernatant from activ ated peripheral blood mononuclear cells (leukocytes) to study the alteratio ns in cellular phenotype, and examined the signaling pathways mediating epi thelial-fibroblast like transdifferentiation. Our hypothesis of the propose d sequence of events leading to tubulointerstitial fibrosis is explained.