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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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FAS and FASL expression in UVA-irradiated T helper cells. T cells were exposed to increasing doses of UVA radiation (0–30 J/cm2). 4 (A)  and 16 (B) h after exposure, cells were analyzed for FAS and FASL surface expression by FACS® analysis as described in Materials and Methods. Data are  given as histograms of cell number versus fluorescence intensity and represent one of five essentially identical experiments.
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Figure 4: FAS and FASL expression in UVA-irradiated T helper cells. T cells were exposed to increasing doses of UVA radiation (0–30 J/cm2). 4 (A) and 16 (B) h after exposure, cells were analyzed for FAS and FASL surface expression by FACS® analysis as described in Materials and Methods. Data are given as histograms of cell number versus fluorescence intensity and represent one of five essentially identical experiments.

Mentions: Before UVA radiation exposure, FASL molecules were not present on the cell surface (Fig. 4), but significant FASL surface expression was detected in UVA-irradiated cells already 4 h after exposure. Ultraviolet A radiation-induced surface FASL expression was dose-dependent and maximal upon exposure of cells to 30 J/cm2 UVA. In contrast to FASL, FAS surface expression remained essentially unaltered upon UVA irradiation (Fig. 4).


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)

FAS and FASL expression in UVA-irradiated T helper cells. T cells were exposed to increasing doses of UVA radiation (0–30 J/cm2). 4 (A)  and 16 (B) h after exposure, cells were analyzed for FAS and FASL surface expression by FACS® analysis as described in Materials and Methods. Data are  given as histograms of cell number versus fluorescence intensity and represent one of five essentially identical experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: FAS and FASL expression in UVA-irradiated T helper cells. T cells were exposed to increasing doses of UVA radiation (0–30 J/cm2). 4 (A) and 16 (B) h after exposure, cells were analyzed for FAS and FASL surface expression by FACS® analysis as described in Materials and Methods. Data are given as histograms of cell number versus fluorescence intensity and represent one of five essentially identical experiments.
Mentions: Before UVA radiation exposure, FASL molecules were not present on the cell surface (Fig. 4), but significant FASL surface expression was detected in UVA-irradiated cells already 4 h after exposure. Ultraviolet A radiation-induced surface FASL expression was dose-dependent and maximal upon exposure of cells to 30 J/cm2 UVA. In contrast to FASL, FAS surface expression remained essentially unaltered upon UVA irradiation (Fig. 4).

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