TLR2 Regulation of Ppargc1a/b in Mice with Staphylococcal aureus Sepsis
Author Information
Author(s): Sweeney Timothy E., Suliman Hagir B., Hollingsworth John W., Welty-Wolf Karen E., Piantadosi Claude A.
Primary Institution: Duke University Medical Center
Hypothesis
The co-activator genes Ppargc1a and Ppargc1b are directly regulated through TLR2 signaling in Staphylococcus aureus sepsis.
Conclusion
Hepatic Ppargc1a and Ppargc1b up-regulation in S. aureus sepsis is independent of MyD88 and MAL and relies on a novel TLR2 pathway involving TRAM, TRIF, and IRF-3/7.
Supporting Evidence
- TLR2−/− mice did not up-regulate Ppargc1a and Ppargc1b in response to S. aureus.
- TLR4−/− mice showed a greater increase in Ppargc1a and Ppargc1b compared to wild type mice.
- Activation of Ppargc1a/b did not require NF-kβ but was dependent on IRF-7.
- TRAM and TRIF were necessary for the induction of Ppargc1a/b in sepsis.
Takeaway
When mice get sick from a bacteria called Staphylococcus aureus, their bodies can turn on special genes that help make energy. This study found that one of the ways this happens is through a specific signaling pathway.
Methodology
The study used various TLR-pathway knockout mice to analyze the expression of Ppargc1a and Ppargc1b in response to S. aureus sepsis.
Limitations
The study primarily focused on mouse models, which may not fully replicate human sepsis responses.
Participant Demographics
Mice of either gender weighing 20–30 grams were used for the studies.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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