title: Gender differences in UV-induced inflammation and immunosuppression in mice reveal male unresponsiveness to UVA radiation.
abstract: Immunosuppression attributed mainly to the UVB (290-320 nm) waveband is a prerequisite for skin cancer development in mice and humans. The contribution of UVA (320-400 nm) is controversial, but in mice UVA irradiation has been found to antagonise immunosuppression by UVB. In other studies of photoimmune regulation, protection mediated via oestrogen receptor-β signalling was identified as a normal endogenous defence in mice, and was shown to depend on UVA irradiation. A gender bias in photoimmune responsiveness was thus suggested, and is tested in this study by comparing the UV-induced inflammatory and immune responses in male and female hairless mice. We report that male mice, which show greater skin thickness than females, developed a less intense but slower resolving sunburn inflammatory oedema, correlated with reduced epidermal expression of pro-inflammatory IL-6 than females following solar simulated UV (SSUV, 290-400 nm) exposure. On the other hand, the contact hypersensitivity reaction (CHS) was more severely suppressed by SSUV in males, correlated with increased epidermal expression of immunosuppressive IL-10. Exposure to the UVB waveband alone, or to cis-urocanic acid, suppressed CHS equally in males and females. However, whereas UVA irradiation induced immunoprotection against either UVB or cis-urocanic acid in females, this protection was significantly reduced or abrogated in males. The results indicate that males are compromised by a relative unresponsiveness to the photoimmune protective effects of UVA, alone or as a component of SSUV. This could explain the known gender bias in skin cancer development in both mice and humans.
authors.affiliation: Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia. vreeve@usyd.edu.au
authors.forename: Vivienne E
authors.initials: VE
authors.lastname: Reeve
authors.forename: Munif
authors.initials: M
authors.lastname: Allanson
authors.forename: Diane
authors.initials: D
authors.lastname: Domanski
authors.forename: Nicole
authors.initials: N
authors.lastname: Painter
mesh_terms: D000818:Animals; D005260:Female; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000209:etiology*; D008297:Male; D051379:Mice; D012737:Sex Factors; D014466:Ultraviolet Rays