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.
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.
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.
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.
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.