Differential ultraviolet-B-induced immunomodulation in XPA, XPC, and CSB DNA repair-deficient mice
| Autor: | Johan Garssen, Adri van Oudenaren, Andre Boonstra, Harry van Steeg, Pieter J. M. Leenen, Miranda R. M. Baert, Gijsbertus T. J. van der Horst, Jan H.J. Hoeijmakers, Huub F. J. Savelkoul |
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| Přispěvatelé: | Immunology, Molecular Genetics |
| Rok vydání: | 2001 |
| Předmět: |
Cellular immunity
Xeroderma pigmentosum DNA Repair DNA damage DNA repair Ultraviolet Rays ultraviolet light Photodermatosis Dermatology Biology Xenopus Proteins Biochemistry chemistry.chemical_compound Interferon-gamma Mice Adjuvants Immunologic Ultraviolet light medicine Animals Poly-ADP-Ribose Binding Proteins Molecular Biology Skin Genetics Mice Knockout Antigen Presentation B-Lymphocytes immunosuppression Hyperplasia Tumor Necrosis Factor-alpha DNA Helicases RNA-Binding Proteins Cell Biology Th1 Cells nucleotide excision repair medicine.disease cytokines Interleukin-10 Xeroderma Pigmentosum Group A Protein DNA-Binding Proteins Mice Inbred C57BL Repressor Proteins DNA Repair Enzymes chemistry Cancer research Lymph Nodes DNA Nucleotide excision repair Transcription Factors |
| Zdroj: | Journal of Investigative Dermatology, 117, 141-146. Nature Publishing Group |
| ISSN: | 0022-202X |
| Popis: | Ultraviolet B irradiation has serious consequences for cellular immunity and can suppress the rejection of skin tumors and the resistance to infectious diseases. DNA damage plays a crucial role in these immunomodulatory effects of ultraviolet B, as impaired repair of ultraviolet-B-induced DNA damage has been shown to cause suppression of cellular immunity. Ultraviolet-B-induced DNA damage is repaired by the nucleotide excision repair mechanism very efficiently. Nucleotide excision repair comprises two subpathways: transcription-coupled and global genome repair. In this study the immunologic consequences of specific nucleotide excision repair defects in three mouse models, XPA, XPC, and CSB mutant mice, were investigated. XPA mice carry a total nucleotide excision repair defect, whereas XPC and CSB mice only lack global genome and transcription-coupled nucleotide excision repair, respectively. Our data demonstrate that cellular immune parameters in XPA, XPC, and CSB mice are normal compared with their wild-type (control) littermates. This may indicate that the reported altered cellular responses in xeroderma pigmentosum patients are not constitutive but could be due to external factors, such as ultraviolet B. Upon exposure to ultraviolet B, only XPA mice are very sensitive to ultraviolet-B-induced inhibition of Th1-mediated contact hypersensitivity responses and interferon-gamma production in skin draining lymph nodes. Lipopolysaccharide-stimulated tumor necrosis factor alpha and interleukin-10 production are significantly augmented in both XPA and CSB mice after ultraviolet B exposure. Lymph node cell numbers were increased very significantly in XPA, mildly increased in CSB, and not in XPC mice. In general XPC mice do not exhibit any indication of enhanced ultraviolet B susceptibility with regard to the immune parameters analyzed. These data suggest that both global genome repair and transcription-coupled repair are needed to prevent immunomodulation by ultraviolet B, whereas transcription-coupled repair is the major DNA repair subpathway of nucleotide excision repair that prevents the acute ultraviolet-B-induced effects such as erythema. |
| Databáze: | OpenAIRE |
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