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...

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Main Authors: XiaoWei Qian, Hao Cheng, XinZhong Chen
Format: Article
Language:English
Published: SAGE Publishing 2019-11-01
Series:Innate Immunity
Online Access:https://doi.org/10.1177/1753425919875796
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author XiaoWei Qian
Hao Cheng
XinZhong Chen
author_facet XiaoWei Qian
Hao Cheng
XinZhong Chen
author_sort XiaoWei Qian
collection DOAJ
description 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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spelling doaj.art-7c1dc125b22541b39e64a8abf9b2a9a92022-12-22T01:21:09ZengSAGE PublishingInnate Immunity1753-42591753-42672019-11-012510.1177/1753425919875796Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsisXiaoWei QianHao ChengXinZhong ChenOur 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.https://doi.org/10.1177/1753425919875796
spellingShingle XiaoWei Qian
Hao Cheng
XinZhong Chen
Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
Innate Immunity
title Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
title_full Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
title_fullStr Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
title_full_unstemmed Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
title_short Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
title_sort transient receptor potential melastatin 2 mediated heme oxygenase 1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis
url https://doi.org/10.1177/1753425919875796
work_keys_str_mv AT xiaoweiqian transientreceptorpotentialmelastatin2mediatedhemeoxygenase1hasaroleforbacterialclearancebyregulatingautophagyinperitonealmacrophagesduringpolymicrobialsepsis
AT haocheng transientreceptorpotentialmelastatin2mediatedhemeoxygenase1hasaroleforbacterialclearancebyregulatingautophagyinperitonealmacrophagesduringpolymicrobialsepsis
AT xinzhongchen transientreceptorpotentialmelastatin2mediatedhemeoxygenase1hasaroleforbacterialclearancebyregulatingautophagyinperitonealmacrophagesduringpolymicrobialsepsis