Molecular mechanisms of UV‐induced apoptosis

Kulms, Dagmar; Schwarz, Thomas

doi:10.1034/j.1600-0781.2000.160501.x

Cited by 281 publications

(223 citation statements)

References 62 publications

(77 reference statements)

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“…In this way, a simple vicious circle can be established, the activity of which might be regulated in several ways. For instance, UV light can precipitate relapses in SLE patients (69), perhaps because of its capacity to induce apoptosis (70) and therefore generation of IFN␣-inducing material.…”

Section: Discussionmentioning

confidence: 99%

Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG

Lövgren

Eloranta

Båve

et al. 2004

Arthritis & Rheumatism

503

411

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Objective. To investigate the release of interferon-␣ (IFN␣)-inducing material by necrotic or apoptotic cells, its properties, and the necessity of autoantibodies from systemic lupus erythematosus (SLE) patients for the interferogenic activity.Methods. U937 monocytic leukemia cells or peripheral blood mononuclear cells (PBMCs) were rendered necrotic by freeze-thawing or apoptotic by treatment with ultraviolet light. Cell culture supernatants from these cells and IgG from SLE patients (SLE IgG) were added to cultures of normal PBMCs or purified plasmacytoid dendritic cells (PDCs). The importance of nucleic acids for IFN␣ induction was investigated by RNase and DNase treatment. The IFN␣ levels were measured by immunoassay.Results. Both necrotic and apoptotic U937 cells released material that, combined with SLE IgG, induced IFN␣ production in PDCs. The release from apoptotic cells occurred with a 16-hour delay, in late apoptosis. Also, normal PBMCs released IFN␣-inducing material, but only during necrosis. The interferogenic activity of the necrotic material required the presence of RNA, while both RNA and DNA were important in the apoptotic material. In both cases, the presence of SLE IgG was necessary, and its activity correlated with the presence of antibodies to RNA-binding proteins, but not anti-DNA antibodies.Conclusion. Necrotic and late apoptotic cells release material that, combined with SLE IgG, induces production of IFN␣ in PDCs. The IFN␣ inducers probably consist of immune complexes (ICs) containing RNA and possibly DNA as essential interferogenic components. The presence of such interferogenic ICs could explain the ongoing production of IFN␣ in SLE and could be of etiopathogenic importance.

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Section: Discussionmentioning

confidence: 99%

Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG

Lövgren

Eloranta

Båve

et al. 2004

Arthritis & Rheumatism

503

411

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“…However, in vitro and in vivo studies have clearly shown the role of p53 and WAF1/p21 and several other genes in UV response. 6,30,31 Studies have clearly shown that p53 mutation is an early event in UV skin carcinogenesis and the clonal expansion of p53-mutated cells leads to development of skin cancer. 4,5 In the present study, using "K5/ODC-transgenic mice," nontransgenic littermates, and SKH-1 hairless mice, we investigated the hypothesis that ODC plays a key role during UVB-mediated responses, including the develop- Figure 1.…”

Section: Resultsmentioning

confidence: 99%

A Definitive Role of Ornithine Decarboxylase in Photocarcinogenesis

Ahmad

Gilliam

Katiyar

et al. 2001

The American Journal of Pathology

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Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component, to human skin is the major cause for more than a million new cases of cutaneous malignancies diagnosed annually in the United States. Photocarcinogenesis, like other cancers, is a multistep process that includes initiation and promotion. A proper understanding of the molecular events occurring during the tumor promotion phase of photocarcinogenesis could lead to the development of novel approaches for the management of skin cancer. Using a transgenic mouse model (K5/ODC mice), which overexpresses the enzyme ornithine decarboxylase (ODC) in hair follicle keratinocytes, we studied the role of this gene in photocarcinogenesis. A single UVB-exposure of 180 mJ/cm 2 to the transgenic mice resulted in a minimal increase in bifold skin thickness and ODC activity. However, in SKH-1 hairless mice, the most common and highly sensitive model for photocarcinogenesis, and in littermate nontransgenic mice, increases in skin thickness and ODC activity were substantial. In long-term experiments, mice were exposed to 180 mJ/cm 2 of UVB radiation three times a week for 2 weeks (tumorinitiating dose). At 30 weeks after this treatment, in two independent experiments, 40% of the K5/ODC transgenic mice exposed to UVB were found to develop epidermal tumors. The tumors were histologically verified as benign papillomas and squamous cell carcinomas. Interestingly, 100% of the transgenic mice also developed >20 pigmented cysts/mouse, which contained keratinocyte material with increased keratinocytic melanization.

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“…Besides its well-known advantages and its indispensable effects on human life, UV radiation, in particular the middle wavelength (UVB, range 290 -320 nm), can be a hazard to human health by inducing cancer, premature skin aging, immunosuppression, inflammation, and cell death (1)(2)(3)(4)(5). Accordingly, the incidence of UV-induced skin cancer is rapidly rising, accounting for Ͼ40% of all human cancers in the United States (6).…”

Section: Il-18mentioning

confidence: 99%

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

Schwarz

Maeda

Ständer

et al. 2006

The Journal of Immunology

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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.

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Molecular mechanisms of UV‐induced apoptosis

Cited by 281 publications

References 62 publications

Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG

Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG

A Definitive Role of Ornithine Decarboxylase in Photocarcinogenesis

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

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