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UV Waveband Interactions
Modulating Photoimmunosuppression
Reeve, Vivienne1
University of Sydney1
Abstract-
The immunosuppressive effect of UV radiation is a pre-requisite for
photocarcinogenesis, and is characterised by dysregulated cytokine patterns,
such as a deficit of IL-12 and IFN-gamma compared with increased expression
of IL-10, and the formation of cis-urocanic acid (UCA) in the epidermis.
In mice the photoimmunosuppression action spectrum peaks in the UVB
(280-320nm) waveband, whereas we show that UVA (320-400nm), which interacts
with skin predominantly via oxidative reactions, is not immunosuppressive
at suberythemal exposures, and moreover provides protection from UVB-immunosuppression.
The pathway to UVA-immunoprotection involves inactivation of cis-UCA,
but is non-functional in IFN-gamma-/- mice. In hairless mouse epidermis,
UVA prevented UVB-induced release of immunosuppressive IL-10, whereas
expression of IFN-gamma and IL-12 was increased. However UVA exposure
also induced cutaneous haem oxygenase (HO), a redox-regulated endogenous
antioxidant enzyme and the major UVA-inducible stress protein identified
in cultured fibroblasts. The inhibition of HO enzyme activity in the
mouse (by injecting the substrate antagonist, tin protoporphyrin, SnPP)
abrogated UVA protection against UVB and cis-UCA. Thus a novel photoimmune
regulatory role for UVA-inducible HO was identified. UVA irradiation
was unable to induce HO activity in the IFN-gamma-/- mouse, demonstrating
the IFN-gamma-dependence of both the UVA-inducible photoimmunoprotection
and HO induction. These studies which used single sequential exposures
to UVA and UVB radiation, subsequently led to studies of exposure of
mice to the simultaneously administered combination of a constant UVB
dose with varying UVA doses. Results indicated that photoimmunosuppression
was reduced as the UVA/UVB ratio increased, and in mice chronically
exposed to such radiation, the severity of the photocarcinogenic outcome
decreased as the UVA intensity was increased. Thus potent inter-regulatory
pathways exist between different UV wavebands which might be exploited
to enhance protection from solar radiation in humans.
Keywords: photoimmunosuppression,
waveband, haem oxygenase, interferon-gamma
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