Increased activation of the transcription factor c-Jun by MAP kinases in monocytes of multiple trauma patients is associated with adverse outcome and mass transfusion

Viktoria Bogner, Veit Stoecklein, Peter Richter, Christian Suren, Daniel Teupser, Karl Georg Kanz, Peter Biberthaler, Wolf Mutschler

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Post-traumatic dysfunction of the immune system is a major source of morbidity and mortality in patients with multiple trauma. The underlying intracellular mechanisms are still incompletely understood. Previous mRNA expression studies in monocytes suggested an involvement of the MAP kinases p38 and JNK and of the transcription factor c-Jun. Therefore, it was the aim of this study to elucidate whether alterations in the protein expression p38 MAPK, JNK, and c-Jun could be linked to PRBC substitution and survival. Materials and methods: Thirty-seven patients with blunt multiple injuries and an ISS > 16 points were enrolled in our study. Blood was drawn on admission and 6, 12, 24, 48, and 72 h after the traumatic event. Monocytes were isolated immediately after sample collection and nuclear protein was extracted and phosphoprotein concentrations were measured. The resulting data were statistically analyzed. Results: An increased activation of MAP kinases and c-Jun could be shown in patients who died from their injuries. Additionally, patients who received PRBC substitution ≥10 units exhibited increased expression of activated MAP kinases and c-Jun. Conclusions: We present a serial, sequential investigation in human monocytes of major trauma patients evaluating the activation of p38 MAPK, JNK and c-Jun in the post-traumatic period. We show that death after trauma and massive PRBC substitution are associated with activation of this pathway. The p38 MAPK, JNK, and c-Jun have well established proinflammatory properties. Therefore, it appears likely that this pathway is involved in the systemic hyperinflammatory states seen after massive PRBC transfusion and multiple trauma.

Original languageEnglish
Pages (from-to)385-389
Number of pages5
JournalJournal of Surgical Research
Volume178
Issue number1
DOIs
StatePublished - Nov 2012

Keywords

  • MAP kinases
  • Mass transfusion
  • Monocytes
  • Multiple trauma
  • c-Jun

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