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

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Abstract

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.

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Acknowledgments

We are grateful to Dr. Harikrishna Nakshatri for helping us establish the EMSA protocol in our lab and we thank Dr. Jeffrey Travers for his helpful comments on the project. This work was supported by a grant from the National Institutes of Health (R01ES11155 to DFS). These studies were funded by a grant from the National Institutes of Health to DFS (R01ES11155).

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Authors and Affiliations

  1. Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Davina A. Lewis & Dan F. Spandau

  2. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Dan F. Spandau

  3. Indiana University Medical Center, Medical Library and Research Building, 975 W. Walnut Street, Room 349, Indianapolis, IN, 46202-5121, USA

    Dan F. Spandau

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  1. Davina A. Lewis
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  2. Dan F. Spandau
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Correspondence to Dan F. Spandau.

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Lewis, D.A., Spandau, D.F. UVB activation of NF-κB in normal human keratinocytes occurs via a unique mechanism. Arch Dermatol Res 299, 93–101 (2007). https://doi.org/10.1007/s00403-006-0729-2

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  • DOI: https://doi.org/10.1007/s00403-006-0729-2

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