Inhibition of intercellular adhesio nmolecule-1 (ICAM-1) expression in ultraviolet B-irradiated human antigen-presenting cells is restored after repair of cyclobutane pyrimidine dimers.
The present study assessed the molecular mechanism underlying ultraviolet (UV) B radiation-induced inhibition of the expression of the adhesion molecule ICAM-1 in human antigen-presenting cells (APC). UVB radiation-induced inhibition of ICAM-I expression in human peripheral blood monocytes was associated with the generation of cyclobutane pyrimidine dimers (CPD). CPD were reduced by 60% after treatment with liposomal packed photolyase, an enzyme which removes CPD after absorption of photoreactivating light. Although incomplete, reduction of CPD was associated with complete restoration of ICAM-1 expression at the mRNA and protein level. Neither reduction of CPD level nor restoration of ICAM-1 expression were observed, if monocytes were treated with empty liposomes, or if they were irradiated with photoreactivating light prior to application of photolyase. DNA damage might also induce soluble mediators capable of autocrine inhibition of ICAM-1 expression. UVB irradiation of monocytes did not induce IL-10 production, but resulted in release of prostaglandin (PG) E2. Treatment of unirradiated monocytes with PGE2 completely inhibited ICAM-1 expression, thus mimicking the UVB effect. Inhibition of monocytic PGE2 production by indomethacin, however, did not restore ICAM-1 expression. These results suggest that formation of CPD is necessary and sufficient for UVB radiation-induced inhibition of ICAM-1 expression. In contrast, PGE2 might serve a paracrine role in UVB radiation-induced immunosuppression.
Grewe
M
M
Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
Stege
H
H
Vink
A
A
Klammer
M
M
Ruzicka
T
T
Roza
L
L
Krutmann
J
J
D000938:Antigen-Presenting Cells / Q000502:physiology / Q000528:radiation effects*; D002478:Cells, Cultured; D000458:Cyanobacteria / Q000201:enzymology; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000008:administration & dosage / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004337:Drug Carriers; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008081:Liposomes; D009000:Monocytes / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
D004337:Drug Carriers; D008081:Liposomes; D011740:Pyrimidine Dimers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D004255:Deoxyribodipyrimidine Photo-Lyase; D015232:Dinoprostone