The role of cis-urocanic acid in UVB-induced suppression of contact hypersensitivity.
Ultraviolet light B (UVB) is well recognized to suppress the contact hypersensitivity (CHS) response and it has been postulated that cis-urocanic acid (UCA) is a mediator of the immunosuppression. This study was designed to examine the effect of UCA on CHS and to clarify its role in UVB-induced immunosuppression in C57BL/6 mice. Intradermal injection of 0.5-50 micrograms cis-UCA into the ear 2 h before DNFB sensitization resulted in a 60-70% reduction of CHS assessed by ear swelling, whereas trans-UCA did not have a significant effect on CHS except at a high dose (50 micrograms) which showed a 20-40% suppression. Intraperitoneal injection of anti-cis-UCA antibody before administration of cis-UCA abrogated the suppression. To examine the effect of UCA on UVB-induced immunosuppression, some mice were pre-treated with anti-cis-UCA antibody and then exposed to UVB (960 J/m2). After 3 days the mice were sensitized either on the irradiated abdominal skin or on the unirradiated dorsal surface of the right ear followed by the challenge on the left ear. The CHS response was significantly suppressed in UVB-irradiated mice both locally (abdominal sensitization, suppression was 45%, P < 0.001) and systemically (ear sensitization, suppression was 53%, P < 0.0025). The CHS response was partially restored in both abdominal sensitized mice and ear sensitized mice by pre-treatment with anti-cis-UCA antibody. These results confirmed the immunosuppressive effects of cis-UCA on CHS and suggest that cis-UCA plays a role in UVB-induced local and systemic immunosuppression.
Kondo
S
S
Division of Dermatology, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Sauder
D N
DN
McKenzie
R C
RC
Fujisawa
H
H
Shivji
G M
GM
El-Ghorr
A
A
Norval
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003877:Dermatitis, Contact / Q000517:prevention & control*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D014560:Urocanic Acid