MODULATORY ROLE OF PLATELET-DERIVED GROWTH-FACTOR ON CYTOKINE-INDUCEDNERVE GROWTH-FACTOR SYNTHESIS IN RAT GLOMERULAR MESANGIAL CELLS

Recent evidence indicates that cytokines are potent inducers of nerve growth factor (NGF) expression in peripheral tissues and in brain. Cul tured rat glomerular mesangial cells respond to interleukin-1 beta (IL -1 beta) and tumour necrosis factor-alpha (TNF-alpha) by increased NGF synthesis. We found that co-stimulation of rat glomerular mesangial c ells with platelet-derived growth factor (PGDF-BB) and IL-1 beta/TNF-a lpha significantly augments the IL-1 beta/TNF-alpha-induced NGF mRNA l evels and NGF synthesis. In contrast, preincubation with PDGF-BB drast ically reduces NGF gene expression and NGF protein synthesis in respon se to IL-1 beta/TNF-alpha stimulation. Thus our results indicate that PDGF-BB is a potent modulator of cytokine-induced NGF expression; its precise action is critically depending on the time at which the PDGF r eceptor is activated.