Urocanic acid analogues and the suppression of the delayed type hypersensitivity response to Herpes simplex virus.
Ultraviolet irradiated urocanic acid (4-imidazoleacrylic acid) containing a mixture of cis- and trans-isomers has been shown previously to induce suppression of the delayed type hypersensitivity (DTH) response to Herpes simplex virus type 1 (HSV-1) in a murine model of infection. The cis-isomer of urocanic acid was prepared and the cis- and trans-isomers of 2-methylurocanic acid. 2-pyrroleacrylic acid, 2-furanacrylic acid, 2-thiopheneacrylic acid, 3-thiopheneacrylic acid as well as dihydrourocanic acid and histamine. Each was applied at concentrations of 1 and 50 micrograms per mouse to the shaved dorsal skin and the mice were infected subcutaneously with HSV 5 h later. After 8-10 days the DTH response to the virus was measured by an ear swelling test. It was found that cis-urocanic acid was effective in suppressing the DTH response at levels of 1 microgram per mouse or less. The cis- and trans-isomers of 2-furanacrylic acid, 2-pyrroleacrylic acid and 2-thiopheneacrylic acid were also effective, with the cis- form generally being more active than trans, and 2-pyrroleacrylic acid being particularly potent. Cis- and trans-3-thiopheneacrylic acid, on the other hand, were only marginally immunosuppressive while neither isomer of 2-methylurocanic acid had any suppressive ability. Dihydrourocanic acid and histamine were also shown to suppress the DTH response. Thus the structural features necessary for urocanic acid and its analogues to act as mediators of UV-induced immunosuppression could be deduced and implications for their mechanism of action discussed.
Norval
M
M
Simpson
T J
TJ
Bardshiri
E
E
Howie
S E
SE
D055598:Chemical Phenomena; D002621:Chemistry; D006968:Hypersensitivity, Delayed / Q000188:drug therapy* / Q000276:immunology; D007093:Imidazoles / Q000627:therapeutic use*; D010778:Photochemotherapy; D018139:Simplexvirus / Q000276:immunology*; D014560:Urocanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*
D007093:Imidazoles; D014560:Urocanic Acid