UVB light induces nuclear factor κB (NFκB) activity independently from chromosomal DNA damage in cell-free cytosolic extracts

Abstract

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 NFκB binding sequence, the effect of UVB light on an NFκB-like binding activity was investigated in a human epidermoid carcinoma cell line (A431). Nuclear factor κB (NFκB) activation in the cytoplasm is known to be due to the dissociation of an inactive NFκB-inhibitor of nuclear factor κB (IκB) complex. Cytosolic extracts from cells harvested shortly after sublethal UVB irradiation showed a UVB dosedependent increase of NFκB binding. The activation was reduced by radical scavenging chemicals, suggesting involvement of reactive oxygen intermediates. NFκB 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 NFκB activation crude, cytosolic protein extracts obtained from unirradiated cells were exposed to UVB light. This in vitro UVB treatment led to activation of an NFκB-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. © 1994.