Differential regulation of nitric oxide synthase-II mRNA by growth factors in rat, bovine, and human retinal pigmented epithelial cells

Retinal pigmented epithelial cells (RPE cells) express the inducible isoform of NO synthase (NOS-II) after stimulation by cytokines and endotoxin. We have attempted to describe and compare the effect of fibroblast growth factor (FGF) and transforming growth factor beta (TCF beta) on NOS-II mRNA level in three different cell species:rat, bovine, and human. Northern blot analysis demonstrated that, in the rat RPE cells, FCF upregulates and TGF beta inhibits NOS-II mRNA accumulation, whereas in the bovine cells, the opposite effect appears. For the human RPE cells, RT-PCR analysis demonstrated that FGF upregulates and TGF beta inhibits NOS-II mRNA accumulation, as in rat cells, even though the effect of TGF beta was weaker. Thus, this study demonstrates that marked differences in growth factors regulating NOS-II occur between species, suggesting fundamental signal transduction differences at some level between rat, human, and cow.