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Effect of combined radiation injury on cell death and inflammation in skin

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Abstract

In the event of a nuclear disaster, the individuals proximal to the source of radiation will be exposed to combined radiation injury. As irradiation delays cutaneous repair, the purpose of this study was to elucidate the effect of combined radiation and burn injury (CRBI) on apoptosis and inflammation at the site of skin injury. Male C57Bl/6 mice were exposed to no injury, thermal injury only, radiation only (1 and 6 Gy) and CRBI (1 and 6 Gy) and euthanized at various times after for skin collection. TUNEL staining revealed that the CRBI 6 Gy group had a delayed and increased apoptotic response. This correlated with decreased recovery of live cells as compared to the other injuries. Similar response was observed when cleaved-caspase-3 immunohistochemical staining was compared between CRBI 6 Gy and thermal injury. TNFR1, caspase 8, Bax and IL-6 mRNA expression revealed that the higher CRBI group had delayed increase in mRNA expression as compared to thermal injury alone. RIPK1 mRNA expression and necrotic cell counts were delayed in the CRBI 6 Gy group to day 5. TNF-α and NFκB expression peaked in the CRBI 6 Gy group at day 1 and was much higher than the other injuries. Also, inflammatory cell counts in the CRBI 6 Gy group were lower at early time points as compared to thermal injury by itself. These data suggest that CRBI delays and exacerbates apoptosis and inflammation in skin as well as increases necrosis thus resulting in delayed wound healing.

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Acknowledgments

This study was funded by the National Institutes of Health (RC1AI080976). Norma Roda and Rachel Livingston are thanked for their help with tissue processing.

Compliance with ethical standards

This study was approved by the Institutional Animal Care and Use Committee (IACUC) of the Keck School of Medicine of the University of Southern California.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. School of Pharmacy, University of Southern California, Los Angeles, CA, USA

    Sachin S. Jadhav, Christopher J. Meeks, Nicholas M. Mordwinkin, Theresa B. Espinoza, Stan G. Louie & Kathleen E. Rodgers

  2. Keck School of Medicine, University of Southern California, 1985 Zonal Avenue, Room 700, Los Angeles, CA, 90089, USA

    Gere S. diZerega

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  1. Sachin S. Jadhav
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  2. Christopher J. Meeks
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  6. Gere S. diZerega
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  7. Kathleen E. Rodgers
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Correspondence to Kathleen E. Rodgers.

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Jadhav, S.S., Meeks, C.J., Mordwinkin, N.M. et al. Effect of combined radiation injury on cell death and inflammation in skin. Apoptosis 20, 892–906 (2015). https://doi.org/10.1007/s10495-015-1116-2

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