Transforming growth factor-beta 2 inhibits interleukin 1 beta-induced expression of inducible nitric oxide synthase in rat renal mesangial cells.
OBJECTIVE
We have investigated whether transforming growth factor beta 2 (TGF-beta 2) influences the expression of inducible nitric oxide synthase (iNOS).


METHODS
Rat renal mesangial cells exposed to the inflammatory cytokine interleukin 1 beta (IL-1 beta).


RESULTS
Addition of TGF-beta 2 dose-dependently suppresses IL-1 beta-induced nitrite formation. Western and Northern blot analyses of mesangial cell extracts reveal that the inhibition of IL-1 beta-induced nitrite formation by TGF-beta 2 is due to decreased iNOS protein and iNOS mRNA steady state levels. Reduction of iNOS mRNA levels is due to decreased transcriptional activity of the iNOS gene under the action of TGF-beta 2 as shown by nuclear run on experiments.


CONCLUSIONS
TGF-beta 2 is a potent inhibitor of iNOS expression acting by reducing the transcriptional activity of the iNOS gene.
Kunz
D
D
Department of Pharmacology, University of Basel, Switzerland.
Walker
G
G
Pfeilschifter
J
J
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004790:Enzyme Induction; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000201:enzymology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019001:Nitric Oxide Synthase