Interdependence between heme oxygenase-1 induction and estrogen-receptor-beta signaling mediates photoimmune protection by UVA radiation in mice.
Previous studies have found that signaling by the estrogen receptor-beta (Er-beta) attenuated solar-simulated UV radiation (SSUV)-induced immunosuppression. This study seeks evidence for a common mechanism for this immunoprotection for both Er-beta signaling and irradiation with the UVA waveband. In Skh:hr-1 hairless mice, the immunoprotection afforded by UVA exposure against subsequent UVB or cis-urocanic acid suppression of contact hypersensitivity (CHS) was abrogated by treatment with the antiestrogen, ICI 182,780. Furthermore, in normal C57BL mice, UVA enrichment of UVA/UVB sources provided protection against UVB-suppressed CHS and upregulated epidermal IL-10 expression, but this protection was inhibited in Er-beta-/- mice. These observations indicated that the immunoprotective response to UVA was dependent on Er-beta signaling. As earlier studies have established that UVA photoimmune protection depends on the induction of the stress enzyme, heme oxygenase (HO)-1, its activity was examined relative to Er-beta. Immunoprotection against SSUV by 17-beta-estradiol was prevented by inhibiting HO enzyme activity; immunoprotection against cis-urocanic acid by carbon monoxide (HO product) was prevented by ICI 182,780. In addition, the HO-1 gene was unresponsive to UVA induction in Er-beta-/- mice. Therefore, HO-1 inducibility and Er-beta signaling are interdependent requisite responses to the UVA waveband for its immunoprotective action against UVB exposure.
Reeve
Vivienne E
VE
Faculty of Veterinary Science, University of Sydney, New South Wales, Australia. vreeve@usyd.edu.au
Allanson
Munif
M
Cho
Jun-Lae
JL
Arun
Sondur J
SJ
Domanski
Diane
D
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology / Q000528:radiation effects*; D016753:Interleukin-10 / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D047629:Estrogen Receptor beta; D008665:Metalloporphyrins; D011524:Protoporphyrins; D012333:RNA, Messenger; D016753:Interleukin-10; D000077267:Fulvestrant; D004958:Estradiol; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D014560:Urocanic Acid