Transforming growth factor-betas block cytokine induction of catalase and xanthine oxidase mRNA levels in cultured rat cardiac cells.
We examined the effects of transforming growth factor-beta (TGF-beta) on the mRNA expression of the antioxidative enzymes, catalase, manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD), as well as the oxidative enzyme, xanthine oxidase (XO), in cultures of cardiomyocytes, cardiac non-myocytes, and fetal bovine heart endothelial cells. TGF-betas alone had little effect on expression of these enzymes, but treatment with a combination of interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha increased expression of MnSOD, catalase, and XO in some cell types with little effect on CuZnSOD expression. When TGF-betas were added along with these inflammatory cytokines there was a return to control levels of catalase expression, as well as a dramatic reduction in XO expression. In fetal bovine heart endothelial cells, treatment with inflammatory cytokines increased XO mRNA expression 11.5-fold and inclusion of TGF-betas reduced this 4-5-fold: effects on XO enzyme activity paralleled those seen on mRNA expression. Similar changes in XO expression were seen in cardiomyocytes. In contrast, TGF-betas did not change cytokine-induced MnSOD expression. All three mammalian isoforms of TGF-beta showed similar effects. In summary, TGF-betas may be able to decrease superoxide anion production and subsequent tissue damage by decreasing levels of XO.
Flanders
K C
KC
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892, USA.
Bhandiwad
A R
AR
Winokur
T S
TS
D000818:Animals; D000831:Animals, Newborn; D002374:Catalase / Q000235:genetics*; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000235:genetics*
D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase