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Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.

Morita A, Werfel T, Stege H, Ahrens C, Karmann K, Grewe M, Grether-Beck S, Ruzicka T, Kapp A, Klotz LO, Sies H, Krutmann J - J. Exp. Med. (1997)

Bottom Line: In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin.In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation.These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.

ABSTRACT
Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.

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Singlet oxygen-induced apoptosis and FASL expression in  human T cells. Human T helper cells were stimulated with increasing concentration of NDPO2 (0–30 mM) or NDP (30 mM) in the absence or  presence of deuterium oxide (90%). After 4 h, the percentage of apoptotic  cells (solid bar) or FASL+ cells (open bar) was determined as described in  Materials and Methods. Data represent one of four essentially identical experiments.
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Figure 7: Singlet oxygen-induced apoptosis and FASL expression in human T cells. Human T helper cells were stimulated with increasing concentration of NDPO2 (0–30 mM) or NDP (30 mM) in the absence or presence of deuterium oxide (90%). After 4 h, the percentage of apoptotic cells (solid bar) or FASL+ cells (open bar) was determined as described in Materials and Methods. Data represent one of four essentially identical experiments.

Mentions: We next assessed whether UVA radiation-induced apoptosis could be mimicked by stimulating unirradiated human T helper cells with singlet oxygen. Singlet oxygen was generated by thermal decomposition of NDPO2 (17). As shown in Fig. 7, singlet oxygen increased FASL surface expression in unirradiated T cells to an extent similar to that observed in UVA-irradiated cells. Similar to FASL surface expression, singlet oxygen generation also induced apoptosis in unirradiated cells (Fig. 7). NDPO2-induced FASL surface expression as well as apoptosis were significantly enhanced, if T cells were stimulated in the presence of deuterium oxide. Treatment of cells with NDP did not induce FASL surface expression or apoptosis. Addition of anti-FAS antibody ZB4 significantly inhibited apoptosis in unirradiated cells, which had been exposed to NDPO2 (Fig. 5).


Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.

Morita A, Werfel T, Stege H, Ahrens C, Karmann K, Grewe M, Grether-Beck S, Ruzicka T, Kapp A, Klotz LO, Sies H, Krutmann J - J. Exp. Med. (1997)

Singlet oxygen-induced apoptosis and FASL expression in  human T cells. Human T helper cells were stimulated with increasing concentration of NDPO2 (0–30 mM) or NDP (30 mM) in the absence or  presence of deuterium oxide (90%). After 4 h, the percentage of apoptotic  cells (solid bar) or FASL+ cells (open bar) was determined as described in  Materials and Methods. Data represent one of four essentially identical experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199141&req=5

Figure 7: Singlet oxygen-induced apoptosis and FASL expression in human T cells. Human T helper cells were stimulated with increasing concentration of NDPO2 (0–30 mM) or NDP (30 mM) in the absence or presence of deuterium oxide (90%). After 4 h, the percentage of apoptotic cells (solid bar) or FASL+ cells (open bar) was determined as described in Materials and Methods. Data represent one of four essentially identical experiments.
Mentions: We next assessed whether UVA radiation-induced apoptosis could be mimicked by stimulating unirradiated human T helper cells with singlet oxygen. Singlet oxygen was generated by thermal decomposition of NDPO2 (17). As shown in Fig. 7, singlet oxygen increased FASL surface expression in unirradiated T cells to an extent similar to that observed in UVA-irradiated cells. Similar to FASL surface expression, singlet oxygen generation also induced apoptosis in unirradiated cells (Fig. 7). NDPO2-induced FASL surface expression as well as apoptosis were significantly enhanced, if T cells were stimulated in the presence of deuterium oxide. Treatment of cells with NDP did not induce FASL surface expression or apoptosis. Addition of anti-FAS antibody ZB4 significantly inhibited apoptosis in unirradiated cells, which had been exposed to NDPO2 (Fig. 5).

Bottom Line: In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin.In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation.These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.

ABSTRACT
Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.

Show MeSH
Related in: MedlinePlus