We previously reported that the transcription factors Stat3 and C/EBPβ synergize to induces the expression of microRNA (miR)-21 and miR-181b to promote MDSC expansion in a mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive stage.
Recently, microRNA-297 (miR-297) and signal transducer and activator of transcription 3 (STAT3) have been demonstrated to be involved in dysfunction of vascular endothelial cells and inflammatory conditions, such as sepsis.
To investigate obesity in mice with hepatic-specific STAT3 inhibition, we randomized mice to a high-fat or normal diet as described above for 6 mo before induction of sepsis.
Expression of the Long Intergenic Non-Coding RNA (lincRNA) of the NED25 Gene Modulates the microRNA-125b, STAT3, Nitric Oxide, and Procalcitonin Signaling Pathways in Patients with Sepsis.
Western blot analysis was performed to confirm whether LPS-induced in vitro sepsis was correlated with the involvement of the Stat3/TLR4 signaling pathway.
In the present study, the role of deleted in liver cancer 1 (DILC), interleukin (IL)‑6, signal transducer and activator of transcription 3 (STAT3), and Toll‑like receptor 4 (TLR4) in the pathogenesis of sepsis was investigated.
All in all, our study demonstrated that miR-34a promoted iNOS secretion from pulmonary macrophages in LPS-induced sepsis suckling rats through activating STAT3 pathway.
Upregulation was dependent on the STAT3/HIF-1α/glycolysis axis, and blocking glycolysis ameliorated increased susceptibility to sepsis in iKIR-treated CLP mice.
We have also demonstrated that P2X7 receptor blockade diminished STAT3 activation in cerebral cortex and hippocampus from septic mice, indicating association of ATP-P2X7-STAT3 signaling axis in SAE during sepsis.
Mechanistically, miR-375 could target Janus kinase 2 (JAK2) and further impaired signal transducer and activator of transcription 3 (STAT3) in sepsis Gr1+CD11b+ MDSC.
Mechanistically, transcription factor Rb phosphorylation supports Stat3 and C/EBPβ accumulation at both miRNA promoters, and C/EBPβ or Stat3 depletion by siRNA in sepsis Gr1<sup>+</sup>CD11b<sup>+</sup> MDSCs inhibits miR-21 and miR-181b expression.
By targeting STAT3-dependent acute-phase changes in the liver, we evaluated the role of liver STAT3 activity in promoting host defense in the context of sepsis and pneumonia.
Collectively, these findings demonstrate that Zn deficiency enhances the acute phase response through up-regulation of the JAK-STAT3 pathway, thereby perpetuating increased inflammation that may lead to increased morbidity and mortality in response to sepsis.