Lack of metallothionein-I and -II exacerbates the immunosuppressive effect of ultraviolet B radiation and cis-urocanic acid in mice.
The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immunosuppressive action of ultraviolet B (UVB; 280-320 nm) radiation has been examined. Mice were exposed to a series of increasing daily UVB doses, each dose administered to the dorsum on 3 consecutive days. Erythema was assessed, and measured as its oedema component by the post-irradiation dorsal skinfold thickness, but there was no effect of the null mutation (MT-/-) observed after 3 x 3.4 kJ/m2 of UVB radiation. Immune function was assessed by the contact hypersensitivity (CHS) response, which was initiated by sensitization on unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal treatments. In comparison with the wild-type MT+/+ mouse, the MT-/- mouse was significantly more immunosuppressed by moderate daily UVB doses (1. 75-5.9 kJ/m2). When topically applied cis-urocanic acid (cis-UCA) replaced UVB radiation as the immunosuppressive agent, contact hypersensitivity in MT-/- mice was again markedly more suppressed than in MT+/+ mice, in a dose-responsive manner. The results infer that MT, which was shown immunohistochemically to be strongly induced in the epidermis of MT+/+ mice, but to be absent in MT-/- epidermis, has the potential to protect from photoimmunosuppression, and that the mechanism of action may be via the inactivation of the epidermal UVB-photoproduct, cis-UCA.
Department of Veterinary Anatomy and Pathology, University of Sydney, New South Wales, Australia.
V E
VE
Reeve
N
N
Nishimura
M
M
Bosnic
A E
AE
Michalska
K H
KH
Choo
D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004487:Edema / Q000503:physiopathology; D004890:Erythema / Q000503:physiopathology; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D008668:Metallothionein / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012867:Skin / Q000378:metabolism; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology*
D008668:Metallothionein; D014560:Urocanic Acid