Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation.

Applegate, Lee Ann; Ley, Ronald D.; Alcalay, Joseph; Kripke, Margaret L.

doi:10.1084/jem.170.4.1117

Cited by 238 publications

(132 citation statements)

References 40 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…UV-induced DNA damage is the major molecular trigger for photoimmunosuppression because reduction of DNA damage is associated with a mitigation of the compromise to the immune system by UV exposure (9,27). In addition, it was recently shown that the well-known antagonism of UV-induced immunosuppression by IL-12 is at least partially due to its capacity to reduce UV-mediated DNA damage (21).…”

Section: Il-18 Prevents Uv-induced Suppression Of the Induction Of Chsmentioning

confidence: 99%

“…This result indicates that IL-12 and IL-18 only share the same effect on preventing UV-induced immunosuppression, whereas IL-18, in contrast to IL-12, is not able to break established tolerance. Because UV-induced immunosuppression can be prevented by reducing DNA damage (9,27), it is obvious that IL-18 like IL-12 appears to prevent immunosuppression via its effect on DNA repair.…”

Section: Il-18 Prevents Uv-induced Suppression Of the Induction Of Chsmentioning

confidence: 99%

See 1 more Smart Citation

IL-18 Reduces Ultraviolet Radiation-Induced DNA Damage and Thereby Affects Photoimmunosuppression

Schwarz

Maeda

Ständer

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

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.

show abstract

Section: Il-18 Prevents Uv-induced Suppression Of the Induction Of Chsmentioning

confidence: 99%

Section: Il-18 Prevents Uv-induced Suppression Of the Induction Of Chsmentioning

confidence: 99%

IL-18 Reduces Ultraviolet Radiation-Induced DNA Damage and Thereby Affects Photoimmunosuppression

Schwarz

Maeda

Ständer

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…UV-induced DNA damage, predominantly in the form of cyclobutane pyrimidine dimers (CPDs) or thymine dimers, has been recognized as an important molecular trigger for the suppression of immune responses (Applegate et al, 1989) and initiation of UV-carcinogenesis (Applegate et al, 1989;Kripke et al, 1992;Yarosh et al, 1992). In turn, accelerated or enhanced removal of UV-induced CPDs through the topical application of the bacterial DNA repair enzyme, T4 endonuclease V, impaired the development of skin tumors in mice exposed to chronic UV radiation .…”

Section: Il-12 Prevents Uv-induced Immunosuppression Through Dna Repamentioning

confidence: 99%

Interleukin-12 and photocarcinogenesis

Katiyar

2007

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

UV radiation induces immunosuppression and inflammatory responses, as well as oxidative stress and DNA damage, in skin cells and these various effects have been implicated in melanoma and nonmelanoma skin cancers, i.e., photocarcinogenesis. The cytokine interleukin (IL)-12 has been shown to possess potent anti-tumor activity in a wide variety of murine tumor models. In this review, we summarize the evidence that IL-12 plays a role in preventing photocarcinogenesis, and present a model of its possible mechanisms of action. Treatment of mice with IL-12 prevents UV-induced immunosuppression in a process mediated by repair of UV-induced damaged DNA. After exposure to the photocarcinogenesis protocol, the development of UV-induced tumors is more rapid and the tumor multiplicity and tumor size are significantly greater in IL-12-deficient or knockout (KO) mice than their wild-type counterparts. IL-12-deficiency in mice enhances the proliferation potential of tumor cells, and this may be one of the reasons for the rapid growth of the tumors and their greater size. The rate of malignant transformation of UV-induced papillomas to carcinomas also is higher in the IL-12 KO mice than in their wild-type counterparts in terms of carcinoma incidence and carcinoma multiplicity. UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) and sunburn cells is lower, or repaired more rapidly, in wild-type mice than IL-12 KO mice. The IL-12-associated reduction in UV-specific CPDs is due to induction of DNA repair, and particularly enhancement of nucleotide-excision repair. We suggest that endogenous stimulation of IL-12 may protect the skin from UV-induced immunosuppression, DNA damage, and, ultimately, the risk of photocarcinogenesis. Taken together, these information suggest that augmentation of IL-12 should be considered as a strategy for the prevention and treatment of photocarcinogenesis.

show abstract

“…Studies by Kripke's team were the first to suggest that DNA (and most likely, the pyrimidine dimer) may be the chromophore for UVB-induced immunosuppression (Applegate et al, 1989), and evidence linking DNA damage with immune modulation has come from studies on XP patients (Suzuki et al, 2001). Trans-UCA is a natural component of the strateum corneum, and UV induces a photoisomeric isomerization of trans-UCA to cis-UCA, which appears to be an initiator of the UV-immunosuppression, although its mechanism of action is still uncertain (Halliday & Rana, 2008;Norval et al, 2008).…”

Section: Immune Response and Photoadaptationmentioning

confidence: 99%

“…In the former, the antigen is applied directly to the irradiated body site soon after UV exposure. In the latter, following UV exposure of one part of the body, the antigen is applied to a distant, non-irradiated body site (Applegate et al, 1989).…”

Section: Immune Response and Photoadaptationmentioning

confidence: 99%