Ultraviolet radiation-induced interleukin 6 release in HeLa cells is mediated via membrane events in a DNA damage-independent way.
Evidence exists that ultraviolet radiation (UV) affects molecular targets in the nucleus or at the cell membrane. UV-induced apoptosis was found to be mediated via DNA damage and activation of death receptors, suggesting that nuclear and membrane effects are not mutually exclusive. To determine whether participation of nuclear and membrane components is also essential for other UV responses, we studied the induction of interleukin-6 (IL-6) by UV. Exposing HeLa cells to UV at 4 degrees C, which inhibits activation of surface receptors, almost completely prevented IL-6 release. Enhanced repair of UV-mediated DNA damage by addition of the DNA repair enzyme photolyase did not affect UV-induced IL-6 production, suggesting that in this case membrane events predominant over nuclear effects. UV-induced IL-6 release is mediated via NFkappaB since the NFkappaB inhibitor MG132 or transfection of cells with a super-repressor form of the NFkappaB inhibitor IkappaB reduced IL-6 release. Transfection with a dominant negative mutant of the signaling protein TRAF-2 reduced IL-6 release upon exposure to UV, indicating that UV-induced IL-6 release is mediated by activation of the tumor necrosis factor receptor-1. These data demonstrate that UV can exert biological effects mainly by affecting cell surface receptors and that this is independent of its ability to induce nuclear DNA damage.
Kulms
D
D
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, D-48149 Münster, Germany.
Pöppelmann
B
B
Schwarz
T
T
D015703:Antigens, CD / Q000502:physiology; D017209:Apoptosis / Q000528:radiation effects*; D002462:Cell Membrane / Q000502:physiology / Q000528:radiation effects*; D002467:Cell Nucleus / Q000502:physiology / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins; D015850:Interleukin-6 / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014466:Ultraviolet Rays
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D015850:Interleukin-6; D007976:Leupeptins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D000072000:NF-KappaB Inhibitor alpha; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde