PMID- 34837868
OWN - NLM
STAT- MEDLINE
DCOM- 20220204
LR  - 20220204
IS  - 1532-8511 (Electronic)
IS  - 1052-3057 (Linking)
VI  - 31
IP  - 1
DP  - 2022 Jan
TI  - RIPK3-Dependent Necroptosis Activates MCP-1-Mediated Inflammation in Mice after 
      Intracerebral Hemorrhage.
PG  - 106213
LID - S1052-3057(21)00618-2 [pii]
LID - 10.1016/j.jstrokecerebrovasdis.2021.106213 [doi]
AB  - BACKGROUND: Recent studies have reported that receptor-interacting protein kinase 
      3 (RIPK3)-dependent necroptosis is related to the pathological process of 
      intracerebral hemorrhage (ICH). Some studies support the view that inhibiting 
      necroptosis is a key mechanism preventing inflammation. Inflammation is a crucial 
      factor contributing to neurological injuries and unfavorable outcomes after ICH. 
      The aim of this study was to clarify the association between necroptosis and 
      monocyte chemoattractant protein-1 (MCP-1)-mediated inflammation and identify a 
      new target for the treatment of ICH. METHODS: An ICH model was established in 
      C57BL/6 mice by injecting collagenase IV into the right basal ganglia. The RIPK3 
      inhibitor GSK872 was administered through intraventricular injection. Then, we 
      assessed brain edema and neurobehavioral function. Western blotting was employed 
      to detect changes in RIPK3, phospho-mixed lineage kinase domain-like protein 
      (p-MLKL), MCP-1, phospho-c-Jun N-terminal kinase (p-JNK) and interleukin 6 (IL-6) 
      levels in the brain tissue. The localization of RIPK3 and MCP-1 was observed 
      using immunofluorescence staining. Co-immunoprecipitation was performed to 
      determine the interaction between RIPK3 and MCP-1. RESULTS: Compared with the 
      sham group, the levels of RIPK3, p-MLKL, MCP-1, p-JNK and IL-6 were increased 
      post-ICH. GSK872 pretreatment significantly reduced RIPK3, p-MLKL, MCP-1, p-JNK 
      and IL-6 expression, accompanied by mitigated cerebral edema and neurobehavioral 
      defects. RIPK3 and MCP-1 colocalized in the perinuclear region after ICH. We 
      detected the formation of the RIPK3-MCP-1 complex in ICH brain tissue. 
      CONCLUSIONS: There exerted an association between RIPK3 and MCP-1. The inhibition 
      of RIPK3 alleviated MCP-1-mediated inflammation following ICH.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Huang, Simei
AU  - Huang S
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wannan Medical College, Wuhu 241000, Anhui, China; 
      Department of Neurology, Wannan Medical College First Affiliated Hospital, 
      Yijishan Hospital, Wuhu 241000, Anhui, China.
FAU - Hu, Wenjie
AU  - Hu W
AD  - Department of Neurology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei 230000, Anhui, China.
FAU - Rao, Dongmei
AU  - Rao D
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wannan Medical College, Wuhu 241000, Anhui, China; 
      Department of Neurology, Wannan Medical College First Affiliated Hospital, 
      Yijishan Hospital, Wuhu 241000, Anhui, China.
FAU - Wu, Xiaodong
AU  - Wu X
AD  - Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Chaohu 
      238001, Anhui, China.
FAU - Bai, Qingqing
AU  - Bai Q
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wannan Medical College, Wuhu 241000, Anhui, China; 
      Department of Neurology, Wannan Medical College First Affiliated Hospital, 
      Yijishan Hospital, Wuhu 241000, Anhui, China.
FAU - Wang, Jingye
AU  - Wang J
AD  - Department of Neurology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei 230000, Anhui, China.
FAU - Chu, Zhaohu
AU  - Chu Z
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wannan Medical College, Wuhu 241000, Anhui, China.
FAU - Xu, Yang
AU  - Xu Y
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wannan Medical College, Wuhu 241000, Anhui, China; 
      Department of Neurology, Wannan Medical College First Affiliated Hospital, 
      Yijishan Hospital, Wuhu 241000, Anhui, China;; Non-coding RNA Research Center of 
      Wannan Medical College, Wuhu 241000, Anhui, China.. Electronic address: 
      southtv@163.com.
LA  - eng
PT  - Journal Article
DEP - 20211124
PL  - United States
TA  - J Stroke Cerebrovasc Dis
JT  - Journal of stroke and cerebrovascular diseases : the official journal of National 
      Stroke Association
JID - 9111633
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ripk3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Brain Edema/etiology
MH  - Cerebral Hemorrhage/*complications
MH  - *Chemokine CCL2
MH  - *Inflammation
MH  - Interleukin-6
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Necroptosis/*drug effects
MH  - Protein Kinases/metabolism
MH  - Receptor-Interacting Protein Serine-Threonine Kinases/*antagonists & 
      inhibitors/metabolism
OTO - NOTNLM
OT  - Inflammation
OT  - Intracerebral hemorrhage
OT  - Monocyte chemoattractant protein-1
OT  - Necroptosis
OT  - Receptor-interacting protein kinase 3
COIS- Declaration of Competing Interest The authors declare that there is no conflict 
      of interest.
EDAT- 2021/11/28 06:00
MHDA- 2022/02/05 06:00
CRDT- 2021/11/27 20:13
PHST- 2021/08/06 00:00 [received]
PHST- 2021/10/13 00:00 [revised]
PHST- 2021/10/31 00:00 [accepted]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2022/02/05 06:00 [medline]
PHST- 2021/11/27 20:13 [entrez]
AID - S1052-3057(21)00618-2 [pii]
AID - 10.1016/j.jstrokecerebrovasdis.2021.106213 [doi]
PST - ppublish
SO  - J Stroke Cerebrovasc Dis. 2022 Jan;31(1):106213. doi: 
      10.1016/j.jstrokecerebrovasdis.2021.106213. Epub 2021 Nov 24.