Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
Identifieur interne : 000311 ( Main/Merge ); précédent : 000310; suivant : 000312Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
Auteurs : Xiaowei Qian [République populaire de Chine] ; Hao Cheng [République populaire de Chine] ; Xinzhong Chen [République populaire de Chine]Source :
- Innate Immunity [ 1753-4259 ] ; 2019.
Abstract
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.
Url:
DOI: 10.1177/1753425919875796
PubMed: 31533549
PubMed Central: 6900664
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<front><div type="abstract" xml:lang="en"><p>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.</p>
</div>
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