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Department of Microbiology and Immunology, Wonkwang University School of Medicine (H.O.P., B.M.C., G.S.O., M.S.L., H.T.C.), and Department of Physiology, Wonkwang University Oriental Medicine (D.G.R.), Iksan, Republic of Korea; Department of Urology, Kosin University Hospital, Busan, Republic of Korea (H.Y.R.); and Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chunchon, Republic of Korea (Y.M.K)
Nitric oxide (NO) has been shown to exert antiproliferative 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. Recent evidence suggests that HO-1 is an important cellular target of NO; whether HO-1 expression contributes to the antiproliferative and/or antiapoptotic effects mediated by NO remains to be investigated. 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 the NO donor sodium nitroprusside (SNP) induced HO-1 expression and that preincubation with SNP suppressed T cell proliferation induced by concanavalin A and apoptosis triggered by anti-Fas antibody. Suppressions of T cell proliferation and apoptosis comparable with SNP were also observed when the T cells were preincubated with the HO-1 inducer cobalt protoporphyrin. A phosphorothioate-linked HO-1 antisense oligonucleotide blocked HO-1 expression, and subsequently abrogated the antiproliferative and antiapoptotic effects of 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.
Address correspondence to: Hun-Taeg Chung, Department of Microbiology and Immunology, Wonkwang University Medical School, 344-2 Shinyong-Dong, Iksan, Chonbug 570-749, Republic of Korea. E-mail: htchung{at}wonkwang.ac.kr
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