Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.
Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.
Wolf
Peter
P
Research Unit for Photodermatology, Department of Dermatology, Medical University Graz, Auenbrugger Platz 8, A-8036 Graz, Austria. peter.wolf@meduni-graz.at
Nghiem
Dat X
DX
Walterscheid
Jeffrey P
JP
Byrne
Scott
S
Matsumura
Yumi
Y
Matsumura
Yasuhiro
Y
Bucana
Cora
C
Ananthaswamy
Honnavara N
HN
Ullrich
Stephen E
SE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005363:Ficusin / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D007165:Immunosuppression Therapy / Q000379:methods; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011701:PUVA Therapy / Q000009:adverse effects / Q000379:methods; D010972:Platelet Activating Factor / Q000276:immunology*; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D016753:Interleukin-10; D005363:Ficusin