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Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
Our previous study indicated an important protective role of transient receptor potential melastatin 2 (TRPM2) in controlling bacterial clearance in macrophages during polymicrobial sepsis by regulating heme oxygenase-1. Autophagy is necessary for macrophages to kill invasive bacteria. In the presen...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900664/ https://www.ncbi.nlm.nih.gov/pubmed/31533549 http://dx.doi.org/10.1177/1753425919875796 |
Sumario: | Our previous study indicated an important protective role of transient receptor potential melastatin 2 (TRPM2) in controlling bacterial clearance in macrophages during polymicrobial sepsis by regulating heme oxygenase-1. Autophagy is necessary for macrophages to kill invasive bacteria. In the present study, TRPM2 knockout (KO) mice show decreased heme oxygenase-1 and autophagy in peritoneal macrophages after caecal ligation and puncture surgery. Caecal ligation and puncture-induced autophagy in peritoneal macrophages is dependent on heme oxygenase-1. TRPM2 KO mice treated with heme oxygenase-1 inducer before caecal ligation and puncture significantly increase autophagy of peritoneal macrophages, bacterial clearance rate and survival rate. In addition, TRPM2 KO mice treated with heme oxygenase-1 inducer before caecal ligation and puncture significantly attenuate organ injury and systemic inflammation. These improvements are reversed by autophagy inhibitor. Therefore, our findings suggest that TRPM2-mediated heme oxygenase-1 has a role for bacterial clearance possibly by regulating autophagy in peritoneal macrophages during polymicrobial sepsis. |
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