Hepatic inflammation after burn injury is associated with necroptotic cell death signaling

Juan Pablo Idrovo, Devin M. Boe, Soncy Kaahui, Weng Lang Yang, Elizabeth J. Kovacs

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BACKGROUND Burn injury still has a high attributable mortality. The elevated mortality rate of severe burns is still concerning. Hepatic inflammation and injury are common after burns and are associated with poor outcomes. Necroptosis is a programmed cell death linked with inflammation. Thus, assessing necroptotic pathways in the liver can lead to new therapeutic modalities to improve mortality after severe burns. METHODS Mice underwent 15% total body surface area burn or sham injury. Three hours after burn, the mice were euthanized to collect blood and livers. Histology, injury markers, genes expression, and tissue protein levels were compared between groups. RESULTS Compared with sham, burned mice had heightened liver inflammatory cell infiltration and edema. Serum aspartate aminotransferase and alanine aminotransferase were increased by 4.9- and 3.4-fold, respectively, in burned mice relative to sham (p < 0.05). Expression of tumor necrosis factor a, interleukin-6, interleukin-1ß, and CXCL1 (KC) genes were elevated in livers of burned mice by 10-, 86-, 10-, and 828-fold, respectively, compared with sham (p < 0.05). Expression of necroptotic genes, namely, receptor-interacting protein kinases 1 and 3, and mixed lineage kinase domain-like in livers of burned mice were increased by 10-, 13-, and 4.5-fold, respectively, relative to sham (p < 0.05). Receptor-interacting protein kinase 1 and phosphorylated mixed lineage kinase domain-like protein levels measured by Western-blot in livers after burn injury were elevated by 22- and 17-fold, respectively, compared with sham (p < 0.05). CONCLUSION Liver damage occurs early after burns in mice and is associated with elevation of proinflammatory cytokines, chemokine, and proteins involved in the necroptotic pathway. This study suggests that necroptosis plays a role in the pathogenesis of liver failure secondary to burn injury.

Original languageEnglish (US)
Pages (from-to)768-774
Number of pages7
JournalJournal of Trauma and Acute Care Surgery
Volume89
Issue number4
DOIs
StatePublished - Oct 1 2020

Keywords

  • Burn
  • inflammation
  • liver
  • mice
  • trauma

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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