Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair.
Induction of apoptosis of keratinocytes by ultraviolet (UV) radiation is a protective phenomenon relevant in limiting the survival of cells with irreparable DNA damage. Changes in UV-induced apoptosis may therefore have significant impact on photocarcinogenesis. We have found that the immunomodulatory cytokine IL-12 suppresses UV-mediated apoptosis of keratinocytes both in vitro and in vivo. IL-12 caused a remarkable reduction in UV-specific DNA lesions which was due to induction of DNA repair. In accordance with this, IL-12 induced the expression of particular components of the nucleotide-excision repair complex. Our results show that cytokines can protect cells from apoptosis induced by DNA-damaging UV radiation by inducing DNA repair, and that nucleotide-excision repair can be manipulated by cytokines.
Schwarz
Agatha
A
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Von-Esmarchstrasse 58, D-48149 Münster, Germany.
Ständer
Sonja
S
Berneburg
Mark
M
Böhm
Markus
M
Kulms
Dagmar
D
van Steeg
Harry
H
Grosse-Heitmeyer
Karin
K
Krutmann
Jean
J
Schwarz
Thomas
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D015603:Keratinocytes / Q000473:pathology* / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000473:pathology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000494:pharmacology; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D018664:Interleukin-12