Immunoprotective haem oxygenase induction by ultraviolet A (320-400 nm) radiation in the mouse is inhibited in interferon-gamma null mice

BACKGROUND: A protective role for the ultraviolet (UV) A waveband against immunosuppression induced by UVB (280-320 nm) radiation has been identified. The mechanism for UVA immunoprotection was found to involve two apparently unrelated mediators, the T-helper-1-associated proinflammatory cytokine interferon (IFN)-gamma and the UVA-induced redox-regulated stress protein, haem oxygenase (HO). OBJECTIVES: To identify a relationship between these two immune regulators. METHODS: The HO response to UVA radiation in the skin and liver was examined in mice with a targeted disruption of the IFN-gamma gene, known to be unresponsive to UVA photoimmunoprotection. Results IFN-gamma null mice did not respond to UVA irradiation with the normal upregulation of HO activity in either the irradiated skin or the liver. Injection of these mice with recombinant IFN-gamma previously shown to restore the UVA-photoimmunoprotective effect, here partially and dose-responsively restored their ability for induction of HO activity in both skin and liver following UVA irradiation. CONCLUSIONS: IFN-gamma appears to be a prerequisite for the immunoprotective induction of HO, although other mediators may also be involved. The UVA responsiveness of HO in an internal organ such as the liver suggests the existence of a soluble UVA-induced mediator from the skin, which may be IFN-gamma.