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 antiproliferative and antiapoptotic effects on human T cells. Heme oxygenase-1 (HO-1), which degrades heme into biliverdin, free iron (Fe(2+)), 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 Fe(2+) donor FeSO(4) 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.
Pae
Hyun-Ock
HO
Department of Microbiology and Immunology, Wonkwang University Medical School, 344-2 Shinyong-Dong, Iksan, Chonbug 570-749, Republic of Korea.
Choi
Byung-Min
BM
Oh
Gi-Su
GS
Lee
Myeong-Su
MS
Ryu
Do-Gon
DG
Rhew
Hyun-Yul
HY
Kim
Yung-Myung
YM
Chung
Hun-Taeg
HT
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002248:Carbon Monoxide / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005290:Ferric Compounds / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism / Q000502:physiology*; D051547:Heme Oxygenase-1; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D019014:fas Receptor / Q000502:physiology
D005290:Ferric Compounds; D008565:Membrane Proteins; D019014:fas Receptor; D009569:Nitric Oxide; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1