UVB light induces nuclear factor kappa B (NF kappa B) activity independently from chromosomal DNA damage in cell-free cytosolic extracts.
It has been shown previously that ultraviolet (UV) light (290-320 nm) activates keratinocytes to release proinflammatory cytokines including interleukin (IL)-6. Because the 5' flanking region of the IL-6 gene contains a consensus NF kappa B binding sequence, the effect of UVB light on an NF kappa B-like binding activity was investigated in a human epidermoid carcinoma cell line (A431). Nuclear factor kappa B (NF kappa B) activation in the cytoplasm is known to be due to the dissociation of an inactive NF kappa B-inhibitor of nuclear factor kappa B (I kappa B) complex. Cytosolic extracts from cells harvested shortly after sublethal UVB irradiation showed a UVB dose-dependent increase of NF kappa B binding. The activation was reduced by radical scavenging chemicals, suggesting involvement of reactive oxygen intermediates. NF kappa B activation has been shown previously to be triggered by DNA lesions induced by UV light. To elucidate whether DNA damage is necessary and sufficient to mediate NF kappa B activation crude, cytosolic protein extracts obtained from unirradiated cells were exposed to UVB light. This in vitro UVB treatment led to activation of an NF kappa B-like binding activity, suggesting an additional signaling pathway independent of chromosomal DNA damage or byproducts of DNA damage. The activation process was dependent on the presence of membranes. The data suggest at least an additional signaling pathway for the early UVB response, including a component of the pathway residing at the cell membrane.
Simon
M M
MM
Ludwig Boltzmann Institute of Cellbiology and Immunobiology, Department of Dermatology, University of Muenster, Germany.
Aragane
Y
Y
Schwarz
A
A
Luger
T A
TA
Schwarz
T
T
D000975:Antioxidants / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D002474:Cell-Free System; D002875:Chromosomes / Q000737:chemistry*; D003600:Cytosol / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D006801:Humans; D016328:NF-kappa B / Q000528:radiation effects*; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D014020:Tissue Extracts / Q000528:radiation effects; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014466:Ultraviolet Rays
D000975:Antioxidants; D016328:NF-kappa B; D014020:Tissue Extracts