Roles of Heme Oxygenase-1 in the Antiproliferative and Antiapoptotic Effects of Nitric Oxide on Jurkat T Cells

Nitric oxide (NO) has been shown to exert anti-proliferative and antiapoptotic effects on human T cells. Heme oxygenase-1 (HO-1), which degrades heme into biliverdin, free iron (Fe2+), and carbon monoxide (CO), has also been known to have antiproliferative and antiapoptotic effects. HO-1 is known as an important cellular target of NO; whether HO-1 expression contributes to the antiproliferative and/or antiapoptotic effects mediated by NO is not clear. In the present study, we examined the effects of NO on HO-1 expression and possible roles of HO-1 in T cell proliferation and apoptosis. Using human Jurkat T cells, we found that NO from sodium nitroprusside (SNP) induced HO-1 expression and suppressed T cell proliferation induced by concanavalin A and apoptosis triggered by anti-Fas antibody. HO-1 inducer, cobalt protoporphyrin CoPP, also showed suppressions of T cell proliferation and apoptosis that were comparable with SNP. Overexpression of the HO-1 gene after transfection into Jurkat T cells resulted in significant decreases in T cell proliferation and apoptosis. The CO donor tricarbonyldichlororuthenium (II) dimer mimicked the antiproliferative effect of SNP, and the Fe2+ donor FeSO4 blocked anti-Fas-induced apoptosis. Taken together, our results suggest that NO induces HO-1 expression in T cells and that suppressions of T cell proliferation and apoptosis afforded by NO are associated with an increased expression of HO-1 by NO.