Heme oxygenase induction mediates the photoimmunoprotective activity of UVA radiation in the mouse.
In contrast to the immunosuppressive potential of UVB (280-320 nm) radiation in experimental animals and humans, UVA (320-400 nm) radiation at environmentally relevant doses appears to be immunologically inert. However, such exposure to UVA radiation has been observed unexpectedly to induce resistance to UVB-induced immunosuppression in mice, by a mechanism resulting in the inactivation of cis-urocanic acid (UCA), an epidermal immunosuppressive UV photoproduct. In this study in mice, we show that the immunoprotective activity of UVA radiation, against the effects of both UVB radiation and cis-UCA, can be attributed to the induction of cutaneous heme oxygenase (HO; EC 1.14.99.3). Cell-mediated immune function was assessed in vivo by the contact hypersensitivity response induced to oxazolone at an unirradiated skin site, and HO enzyme activity was measured in cutaneous microsomal preparations from treated mice. There was a progressive increase in HO enzyme activity for at least 3 days after UVA irradiation. However HO activity, both constitutive and UVA radiation-induced, was sensitive to the effects of injecting mice with the specific HO inhibitor, tin protoporphyrin (Sn [IV] protoporphyrin IX; SnPP). We observed, in addition, that in SnPP-injected mice, the immunoprotective effect of UVA radiation against either UVB radiation or cis-UCA was abrogated. Because SnPP injection did not affect normal contact hypersensitivity responsiveness but did inhibit the constitutive HO enzyme activity, it appeared that only the inducible HO was active in modulating immune function. This finding indicates that UVA-induced HO activity is a major player in the skin defenses against UVB immunosuppression.
Reeve
V E
VE
Department of Veterinary Anatomy and Pathology, University of Sydney, N.S.W. 2006, Sydney, Australia. v.reeve@vetp.usyd.edu.au
Tyrrell
R M
RM
D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology*; D004790:Enzyme Induction / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008812:Mice, Hairless; D008861:Microsomes / Q000201:enzymology*; D011524:Protoporphyrins / Q000494:pharmacology; D012867:Skin / Q000201:enzymology* / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000276:immunology* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D014560:Urocanic Acid