Transforming Growth Factor-βs Block Cytokine Induction of Catalase and Xanthine Oxidase mRNA Levels in Cultured Rat Cardiac Cells

We examined the effects of transforming growth factor-β(TGF-β) 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-βs alone had little effect on expression of these enzymes, but treatment with a combination of interleukin-1β, interferon-γ, and tumor necrosis factor-αincreased expression of MnSOD, catalase, and XO in some cell types with little effect on CuZnSOD expression. When TGF-βs 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-βs 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-βs did not change cytokine-induced MnSOD expression. All three mammalian isoforms of TGF-βshowed similar effects. In summary, TGF-βs may be able to decrease superoxide anion production and subsequent tissue damage by decreasing levels of XO.