SwePub - sökning: WFRF:(Lehmann R.)

Numrering	Referens	Omslagsbild	Hitta
1.	JANSSENTIMMEN, U, et al. (författare) 5-lipoxygenase expression in cultured human keratinocytes 1995 Ingår i: Advances in prostaglandin, thromboxane, and leukotriene research. - 0732-8141. ; 23, s. 329-331 Tidskriftsartikel (refereegranskat)
2.	Westendorp, Mo, et al. (författare) Hiv-1 Tat Potentiates Tnf-Induced Nf-Kappa-B Activation and Cytotoxicity 1995 Ingår i: EMBO Journal. - 0261-4189 .- 1460-2075. ; 14:3, s. 546-554 Tidskriftsartikel (refereegranskat)abstract This study demonstrates that human immunodeficiency virus type 1 (HTV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HTV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein, TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat(1-72)), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio. They further imply a distinct mechanism of Mn-SOD suppression as compared,vith HIV-1 LTR transactivation by Tat. Taken together, our data suggest that Tat expressed in HIV-1-infected cells and Tat taken up by non-infected cells modulates TNF activity by altering the cellular redox state. These findings may be relevant for HIV-1 replication and for T cell depletion in acquired immune deficiency syndrome.

Westendorp, Mo, et al. (författare)
Hiv-1 Tat Potentiates Tnf-Induced Nf-Kappa-B Activation and Cytotoxicity
1995
Ingår i: EMBO Journal. - 0261-4189 .- 1460-2075. ; 14:3, s. 546-554
Tidskriftsartikel (refereegranskat)abstract
- This study demonstrates that human immunodeficiency virus type 1 (HTV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HTV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein, TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat(1-72)), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio. They further imply a distinct mechanism of Mn-SOD suppression as compared,vith HIV-1 LTR transactivation by Tat. Taken together, our data suggest that Tat expressed in HIV-1-infected cells and Tat taken up by non-infected cells modulates TNF activity by altering the cellular redox state. These findings may be relevant for HIV-1 replication and for T cell depletion in acquired immune deficiency syndrome.

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