Ultraviolet A (320-400 nm) modulation of ultraviolet B (290-320 nm)-induced immune suppression is mediated by carbon monoxide.
Accumulating evidence suggests that suberythemogenic ultraviolet A (UVA) (320-400 nm) exposure protects against the immunosuppressive effect of ultraviolet B (290-320 nm) radiation or its epidermal photoproduct, cis-urocanic acid (cis-UCA). In skin, UVA photoimmunoprotection is mediated by the inducible antioxidant stress enzyme, heme oxygenase-1 (HO-1), which degrades heme into carbon monoxide (CO), iron, and biliverdin (reduced to bilirubin), and is important for cell survival under conditions of oxidative stress. The identity of the HO enzymatic product(s) that provide the immunoprotection is unknown. Here we examine the potential of CO to fulfill this role in hairless mouse skin, utilizing a novel CO-releasing molecule (CO-RM) to deliver CO to the skin topically. The CO-RM released CO gradually from the lotion vehicle during 3 h following its preparation, and between 50 and 500 microM, concentration-dependently protected mice against the suppression of contact hypersensitivity by either solar-simulated UV radiation (SSUVR) or cis-UCA, whereas aged CO-depleted CO-RM was inactive. Thus, the CO-RM treatment mimicked UVA-photoimmunoprotection, and identified HO-released CO as the protective mediator, providing evidence that the murine cutaneous immune system is modulated by this gaseous messenger. Preliminary evidence for involvement of guanylyl cyclase was obtained by treatment of the mouse with its specific inhibitor 1H-(1,2,4)oxadiazolo-(4,3-1)quinoxaline-1-one, which abrogated UVA photoimmunoprotection.
Allanson
Munif
M
Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia.
Reeve
Vivienne E
VE
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007108:Immune Tolerance / Q000528:radiation effects*; D051379:Mice; D008812:Mice, Hairless; D009942:Organometallic Compounds / Q000494:pharmacology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D048051:p38 Mitogen-Activated Protein Kinases; D006162:Guanylate Cyclase; D014560:Urocanic Acid