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Archives of Dermatological Research

, Volume 305, Issue 9, pp 805–815 | Cite as

Ultraviolet light exposure stimulates HMGB1 release by keratinocytes

  • Kelly E. Johnson
  • Brian C. Wulff
  • Tatiana M. Oberyszyn
  • Traci A. Wilgus
Original Paper

Abstract

The primary cause of non-melanoma skin cancer is ultraviolet (UV) light from the sun. Many studies have demonstrated that cutaneous inflammation resulting from UV exposure is important for the development of skin cancer. In fact, anti-inflammatory drugs have been shown to be effective in preventing skin cancer in animal models and in clinical trials. One new class of inflammatory mediators that could regulate UV-induced inflammation and skin carcinogenesis is alarmins. Alarmins are endogenous molecules that act as potent pro-inflammatory mediators when they are released by cells or accumulate extracellularly. The purpose of the current studies was to examine the expression and release of the alarmin high mobility group box 1 (HMGB1) after acute and chronic UV irradiation. Acute UV exposure stimulated the release of HMGB1 in cultured human keratinocytes and epidermal keratinocytes in murine skin. HMGB1 release correlated with pro-inflammatory cytokine production in vitro and inflammatory cell infiltration in vivo. HMGB1 was also examined in tumors arising in chronically irradiated murine skin. HMGB1 protein expression in low grade, benign papillomas was similar to adjacent skin. However, HMGB1 staining was more widespread with a higher number of HMGB1-positive cells observed in high grade papillomas and malignant tumors. Overall, the data suggest that HMGB1 may be an important regulator of UV-induced cutaneous inflammation and tumor formation. Additional studies are needed to assess whether targeting HMGB1 would be a useful strategy to prevent tumors from developing in response to chronic UV exposure.

Keywords

Skin Inflammation Tumor Squamous cell carcinoma Non-melanoma skin cancer 

Notes

Acknowledgments

The authors are supported in part by the following grants from the National Institutes of Health: R01CA109204 (TMO), R01CA127109 (TAW) and R21ES020462 (TAW).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Kelly E. Johnson
    • 1
  • Brian C. Wulff
    • 1
  • Tatiana M. Oberyszyn
    • 1
  • Traci A. Wilgus
    • 1
  1. 1.Department of PathologyThe Ohio State UniversityColumbusUSA

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