Downregulation of protein disulfide isomerase in sepsis and its role in tumor necrosis factor-alpha release
2008

The Role of Protein Disulfide Isomerase in Sepsis

publication Evidence: moderate

Author Information

Author(s): Zhou Mian, Jacob Asha, Ho Natalie, Miksa Michael, Wu Rongqian, Maitra Subir R, Wang Ping

Primary Institution: The Feinstein Institute for Medical Research

Hypothesis

Sepsis downregulates PDI expression and the inhibition of PDI promotes proinflammatory cytokine production.

Conclusion

Downregulation of PDI by sepsis significantly increases proinflammatory cytokine production.

Supporting Evidence

  • PDI gene expression was significantly decreased by 28% and 69% at 20 hours after CLP or LPS infusion.
  • LPS decreased PDI protein expression by 33% in RAW 264.7 cells.
  • Bacitracin significantly increased TNF-α gene expression and release in a dose-dependent manner.
  • Transfection of RAW 264.7 cells with PDI siRNA caused a 3.19-fold increase in TNF-α release.

Takeaway

When the body is fighting sepsis, a protein called PDI gets lower, which makes the body produce more harmful substances that can cause more damage.

Methodology

Adult male rats were subjected to sepsis by cecal ligation and puncture or endotoxemia, and PDI gene expression was measured in hepatic tissues and macrophage-like cells.

Participant Demographics

Adult male Sprague-Dawley rats (275 to 325 g)

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/cc6977

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