Article Text

PDF
GW24-e0805 Mesenchymal Stem Cells down-regulates MIF expression on myocardium in septic mice
  1. Xiong Yan,
  2. Xu Jia,
  3. Zhan Wei,
  4. Jiang Ren,
  5. Zhan Hong
  1. The First Affiliated Hospital of Sun Yat-Sen University

Abstract

Objectives As a novel anti-inflammationary and immuno-regulatory factor, Mesenchymal Stem Cells (MSCs) have recently been applied to treat septic animals in experimental research. Our previous results have shown that MSCs decreased the mortality caused by sepsis, but the exact mechanisms underlying its beneficial effects are not well defined. Since inflammationary injury induced by Migration Inhibitory Factor (MIF), as a late-stage pro-inflammationary factor, is significantly expressed in septic myocardium, we hypothesised that intervention of MSCs could down-regulate its expression on myocardium in septic mice, contributing to its protective outcomes on sepsis. In present study, we aimed to investigate the influence of MSCs on cardiomyocytic MIF expression during sepsis in BALB/c mice.

Methods One hundred and Eighty BALB/c mice were randomly assigned into three groups: the sham group (sham group, n = 60), the sepic control group (septic group, n = 60) and the septic MSCs interventing group (septic + MSCs group, n = 60). Sepsis was induced by cecal ligation puncture in mice of the later two groups, while the mice in septic + MSCs group were treated intravenously with 2 x 106 MSCs once a day for three days before cecal ligation puncture. Serum MIF levels, macroscopic and microscopic cardiomyocytic changes were evaluated 12 h (n = 10), 24 h (n = 10), 36 h (n = 10), 48 h (n = 10), 60 h (n = 10) and 72 h (n = 10) post puncture. The levels of MIF mRNA and protein expression in myocardium were detected at the same time points as above by RT-PCR, Immunohistochemical staining and Western Blot, respectively.

Results Sepsis caused apparent damages to myocardium in mice with cecal ligation puncture. Compared with sham group and septic group, MSCs attenuated the macroscopic and microscopic injuries in myocardium of septic mice, while serum MIF concentrations at 12 h, 24 h, 36 h, 48 h, 60 h and 72 h post puncture were significantly suppressed following MSCs intervention. The mRNA and protein expression of MIF in myocardium were significantly lower in the septic + MSCs group than in the septic group at the same time points as above, but still higher than the sham group (p < 0.05).

Conclusions It is concluded that elevated MIF expression in myocardium may play an important role in pathogenesis of sepsis; MSCs may be taken as a protective option for sepsis treatment; Transcriptional down-regulation of MIF in cardiomyocytes may be one of the molecular mechanisms contributing to the beneficial outcomes following MSCs intervention.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.