AI Article Synopsis
- The study investigates how Oridonin (Ori), an inhibitor of NLRP3, affects liver ischemia reperfusion injury (IRI) by targeting macrophage pyroptosis, a form of programmed cell death.
- In experiments using mice and liver macrophages, Ori was found to reduce pyroptosis and liver damage by disrupting the interaction between PKM2 and NLRP3 during hypoxia/reoxygenation conditions.
- The results suggest that Ori has protective qualities against liver IRI, making it a possible new treatment option by targeting the PKM2/NLRP3 pathway.
Article Abstract
Background: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown.
Methods: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA.
Results: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenation（H/R）-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI.
Conclusion: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.
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| http://dx.doi.org/10.1016/j.cellimm.2024.104838 | DOI Listing |
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