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Itaconate ameliorates methicillin-resistant Staphylococcus aureus-induced acute lung injury through the Nrf2/ARE pathway
- Source :
- Ann Transl Med
- Publication Year :
- 2021
- Publisher :
- AME Publishing Company, 2021.
-
Abstract
- Background Methicillin-resistant Staphylococcus aureus (MRSA) are a critical predisposing factor of sepsis in the clinic. As a product of human energy metabolism and immune response, itaconate can effectively reduce inflammation in the body. This research employed 4-octyl itaconate (4-OI) to illustrate that itaconate exerted anti-inflammatory effects to protect the body from acute lung injury (ALI) induced by MRSA. Methods HE staining and immunohistochemistry are used to evaluate the MRSA-induced ALI in mice. WB and qPCR were used to verify the effect of 4-OI on inflammation and oxidative stress caused by MRSA. Molecular docking was used to verify the binding sites of 4-OI and Keap1. Results We demonstrated that 4-OI treatment increased the survival ratio, attenuated the pathological damage, inhibited neutrophil infiltration, and reduced lung bacterial burden in the mouse MRSA pneumonia model. 4-OI decreased the expression of inflammatory factors by stimulating the Nrf2 in vivo and in vitro. Furthermore, 4-OI exerted its effect by promoting nuclear transport of Nrf2 in vitro. The results of molecular docking indicated that 4-OI bound to the pocket of Keap1 and exerted a stable interaction. Both Nrf2 inhibitors (ML385) and Nrf2-/- mice abolished the protective effect of 4-OI on MRSA-induced inflammation both in vitro and in vivo. Conclusions 4-OI prevents lung damage caused by MRSA bacteremia via activating Nrf2/ARE pathway.
- Subjects :
- 0301 basic medicine
business.industry
Inflammation
General Medicine
Lung injury
Pharmacology
respiratory system
medicine.disease
medicine.disease_cause
In vitro
Sepsis
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Immune system
Staphylococcus aureus
In vivo
030220 oncology & carcinogenesis
medicine
Original Article
medicine.symptom
business
Oxidative stress
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Ann Transl Med
- Accession number :
- edsair.doi.dedup.....f17f092582ffe1d9181892948f0ae634