UVB activation of NF-κB in normal human keratinocytes occurs via a unique mechanism

The transcription factor nuclear factor-κB (NF-κB) is comprised of a family of proteins that are implicated in a wide variety of cellular functions, including the control of cell proliferation, cell survival, and cellular differentiation. Although NF-κB is activated in response to inflammatory signals or cellular stress, in the skin NF-κB is also implicated to play a role in normal epidermal homeostasis. Often the cellular consequences of NF-κB activation are dependent on the specific triggering stimuli. Thus, we have compared the activation mechanism and the function of NF-κB following two common stimuli of normal human keratinocytes, inflammatory mediators (tumor necrosis factor alpha (TNFα)), and cellular stress (ultraviolet light B (UVB) irradiation). These experiments indicate that although both TNFα and UVB stimulate NF-κB DNA-binding activity in normal human keratinocytes, the mechanisms of NF-κB activation by each stimulus is different. In contrast to the NF-κB response following TNFα, activation of NF-κB by UVB is independent of IκBα degradation. Analyses of NF-κB-dependent gene expression following TNFα or UVB treatment demonstrate that each of these stimulatory signals results in a specific subset of genes that are activated or repressed. These studies provide further evidence of the stimuli and cell-type specific nature of NF-κB function.