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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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UVA radiation and NDPO2 induced T cell apoptosis. T cells  were preincubated in the presence of anti-Fas antibody ZB4 (1 μg/ml)  (open bar) or an isotype control antibody (solid bar) for 1 h at 37°C. Cells  were then exposed to UVA radiation (30 J/cm2) or NDPO2 (15 mM).  After 4 h, the percentage of apoptotic cells was determined using the  TUNEL method as described in Materials and Methods. Data represent  mean ± SD of six experiments.
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Figure 5: UVA radiation and NDPO2 induced T cell apoptosis. T cells were preincubated in the presence of anti-Fas antibody ZB4 (1 μg/ml) (open bar) or an isotype control antibody (solid bar) for 1 h at 37°C. Cells were then exposed to UVA radiation (30 J/cm2) or NDPO2 (15 mM). After 4 h, the percentage of apoptotic cells was determined using the TUNEL method as described in Materials and Methods. Data represent mean ± SD of six experiments.

Mentions: In atopen-specific human T helper cells, in vitro UVA irradiation induced apoptosis (Fig. 3, see also Figs. 5, 6). Significant apoptosis was already detectable 4 h after exposure, reaching a maximum 24 h after irradiation with 30 J/cm2 UVA radiation (Fig. 3 and data not shown).


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)

UVA radiation and NDPO2 induced T cell apoptosis. T cells  were preincubated in the presence of anti-Fas antibody ZB4 (1 μg/ml)  (open bar) or an isotype control antibody (solid bar) for 1 h at 37°C. Cells  were then exposed to UVA radiation (30 J/cm2) or NDPO2 (15 mM).  After 4 h, the percentage of apoptotic cells was determined using the  TUNEL method as described in Materials and Methods. Data represent  mean ± SD of six experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: UVA radiation and NDPO2 induced T cell apoptosis. T cells were preincubated in the presence of anti-Fas antibody ZB4 (1 μg/ml) (open bar) or an isotype control antibody (solid bar) for 1 h at 37°C. Cells were then exposed to UVA radiation (30 J/cm2) or NDPO2 (15 mM). After 4 h, the percentage of apoptotic cells was determined using the TUNEL method as described in Materials and Methods. Data represent mean ± SD of six experiments.
Mentions: In atopen-specific human T helper cells, in vitro UVA irradiation induced apoptosis (Fig. 3, see also Figs. 5, 6). Significant apoptosis was already detectable 4 h after exposure, reaching a maximum 24 h after irradiation with 30 J/cm2 UVA radiation (Fig. 3 and data not shown).

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