Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.
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.
Morita
A
A
Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.
Werfel
T
T
Stege
H
H
Ahrens
C
C
Karmann
K
K
Grewe
M
M
Grether-Beck
S
S
Ruzicka
T
T
Kapp
A
A
Klotz
L O
LO
Sies
H
H
Krutmann
J
J
D019138:Antibodies, Blocking / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000532:radiotherapy; D003903:Deuterium / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000528:radiation effects; D009284:Naphthols / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D026082:Singlet Oxygen; D019810:Sodium Azide / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects*; D014467:Ultraviolet Therapy; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D009284:Naphthols; D019014:fas Receptor; D026082:Singlet Oxygen; D019810:Sodium Azide; C058008:3,3'-(1,4-naphthylidene)diproprionate; D003903:Deuterium; D010100:Oxygen