IL-18 reduces ultraviolet radiation-induced DNA damage and thereby affects photoimmunosuppression.
UV-induced DNA damage has been recognized as the major molecular trigger for photoimmunosuppression. IL-12 prevents UV-induced immunosuppression via its recently discovered capacity to reduce DNA damage presumably via induction of DNA repair. Because IL-18 shares some biological activities with IL-12 we studied the effect of IL-18 on UV-induced DNA damage and immunosuppression. IL-18 reduced UV-induced apoptosis of keratinocytes and supported long-term cell survival on UV exposure. Injection of IL-18 into mice that were exposed to UV radiation significantly lowered the number of apoptotic keratinocytes. Accordingly, radiation immunohistochemistry revealed reduced amounts of DNA damage in epidermal cells upon injection of IL-18. These effects were not observed in DNA repair-deficient (XpaKO) mice, indicating that IL-18 like IL-12 reduces DNA damage via DNA repair. UV-mediated suppression of the induction of contact hypersensitivity, which is known to be primarily triggered by DNA damage, was prevented upon injection of IL-18 before UV exposure in wild-type but not in XpaKO mice. In contrast to IL-12, IL-18 was not able either in wild-type or in XpaKO mice to break UV-induced immunotolerance that is mediated via regulatory T cells rather than in a DNA damage-dependent fashion. This result indicates that IL-12 is still unique in its capacity to restore immune responses because of its effect on regulatory T cells. Together, these data identify IL-18 as a further cytokine that exhibits the capacity to affect DNA repair. Though being primarily a proinflammatory cytokine through this capacity, IL-18 can also foster an immune response that is suppressed by UV radiation.
Schwarz
Agatha
A
Department of Dermatology, University Kiel, Kiel, Germany.
Maeda
Akira
A
Ständer
Sonja
S
van Steeg
Harry
H
Schwarz
Thomas
T
D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000528:radiation effects; D002460:Cell Line; D004249:DNA Damage / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000528:radiation effects; D007165:Immunosuppression Therapy; D020382:Interleukin-18 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
D020382:Interleukin-18; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse