Interdependence between Heme Oxygenase-1 Induction and Estrogen-Receptor-β Signaling Mediates Photoimmune Protection by UVA Radiation in Mice

Previous studies have found that signaling by the estrogen receptor-β (Er-β) attenuated solar-simulated UV radiation (SSUV)-induced immunosuppression. This study seeks evidence for a common mechanism for this immunoprotection for both Er-β 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-β-/- mice. These observations indicated that the immunoprotective response to UVA was dependent on Er-β 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-β. Immunoprotection against SSUV by 17-β-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-β-/- mice. Therefore, HO-1 inducibility and Er-β signaling are interdependent requisite responses to the UVA waveband for its immunoprotective action against UVB exposure.