title: UVB activation of NF-kappaB in normal human keratinocytes occurs via a unique mechanism.
abstract: The transcription factor nuclear factor-kappaB (NF-kappaB) 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-kappaB is activated in response to inflammatory signals or cellular stress, in the skin NF-kappaB is also implicated to play a role in normal epidermal homeostasis. Often the cellular consequences of NF-kappaB activation are dependent on the specific triggering stimuli. Thus, we have compared the activation mechanism and the function of NF-kappaB following two common stimuli of normal human keratinocytes, inflammatory mediators (tumor necrosis factor alpha (TNFalpha)), and cellular stress (ultraviolet light B (UVB) irradiation). These experiments indicate that although both TNFalpha and UVB stimulate NF-kappaB DNA-binding activity in normal human keratinocytes, the mechanisms of NF-kappaB activation by each stimulus is different. In contrast to the NF-kappaB response following TNFalpha, activation of NF-kappaB by UVB is independent of Ikappa Balpha degradation. Analyses of NF-kappaB-dependent gene expression following TNFalpha 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-kappaB function.
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Davina A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Dan F
authors.initials: DF
authors.lastname: Spandau
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D048051:p38 Mitogen-Activated Protein Kinases