Transforming growth factor-β2 inhibits interleukin 1β-induced expression of inducible nitric oxide synthase in rat renal mesangial cells

Abstract.

Objective and Design: We have investigated whether transforming growth factor β₂ (TGF-β₂) influences the expression of inducible nitric oxide synthase (iNOS).¶Material: Rat renal mesangial cells exposed to the inflammatory cytokine interleukin 1β (IL-1β).¶Results: Addition of TGF-β₂ dose-dependently suppresses IL-1β-induced nitrite formation. Western and Northern blot analyses of mesangial cell extracts reveal that the inhibition of IL-1β-induced nitrite formation by TGF-β₂ 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-β₂ as shown by nuclear run on experiments.¶Conclusions: TGF-β₂ is a potent inhibitor of iNOS expression acting by reducing the transcriptional activity of the iNOS gene.