Kf. Beck et al., POTENTIATION OF NITRIC-OXIDE SYNTHASE EXPRESSION BY SUPEROXIDE IN INTERLEUKIN 1-BETA-STIMULATED RAT MESANGIAL CELLS, FEBS letters, 435(1), 1998, pp. 35-38
Exposure of mesangial cells to superoxide, generated by the hypoxanthi
ne/xanthine oxidase system or by the redox cycler 2,3-dimethoxy-1,4-na
phthoquinone caused a concentration-dependent amplification of interle
ukin (IL)-1 beta-stimulated nitrite production. The effect of superoxi
de was accompanied by an increase in inducible nitric oxide synthase (
iNOS) protein and iNOS mRNA levels, Incubation of mesangial cells with
superoxide alone did not induce iNOS expression. To elucidate whether
the increase of iNOS expression is due to transcriptional upregulatio
n we fused a 4.5-kb genomic iNOS fragment that contains the transcript
ional start site of the rat iNOS gene to a luciferase reporter gene. I
n transient transfection studies, superoxide caused a 10-fold augmenta
tion of iNOS promoter activity in IL-1 beta-challenged mesangial cells
. Our data identify superoxide as a co-stimulatory factor amplifying c
ytokine-induced iNOS gene expression and subsequent nitric oxide (NO)
synthesis. (C) 1998 Federation of European Biochemical Societies.