STAT3 decoy oligodeoxynucleotides improve end‐organ tissue injury and survival in septic mice

Abstract

STAT3 serves as a key transcription factor in both immunity and inflammatory pathways. We examined whether in vivo introduction of STAT3 decoy oligodeoxynucleotides (ODNs) is beneficial in reducing septic end‐organ injury. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in mice. STAT3 was rapidly activated in major end‐organ tissues following CLP, which was accompanied by activation of the upstream kinase JAK2. Transfection of STAT3 decoy ODNs significantly improved histopathological changes in lung, liver, kidney, and heart tissues. STAT3 decoy ODN transfection downregulated pro‐inflammatory cytokine/chemokine overproduction and reduced the increases in tissue and serum levels of HMGB1 in CLP mice. These beneficial effects of STAT3 decoy ODNs led to s significant survival advantage in mice after CLP. Our results indicate a detrimental role of STAT3 in the sepsis pathophysiology and the potential usefulness of STAT3 decoy ODNs for sepsis therapy.Support or Funding InformationGrants‐in‐Aid for Scientific Research from Japan Society for Promotion of Science (17K08586, 19H03757)