PMID- 31402118
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 518
IP  - 1
DP  - 2019 Oct 8
TI  - Rab GTPase 21 mediates caerulin-induced TRAF3-MKK3-p38 activation and acute 
      pancreatitis response.
PG  - 50-58
LID - S0006-291X(19)31509-8 [pii]
LID - 10.1016/j.bbrc.2019.08.007 [doi]
AB  - Acute pancreatitis (AP) is a severe inflammatory disease. Caerulin induces 
      significant pro-inflammatory responses in macrophages, causing serve damage to 
      pancreatic acinar cells. The potential role of Rab GTPase 21 (Rab21) in this 
      process was tested in this study. In murine bone marrow-derived macrophages 
      (BMDMs), caerulin induced Rab21-TRAF3-MKK3 complex association. Rab21 silencing 
      (by targeted shRNAs) or knockout (by CRISPR/Cas9 method) largely inhibited 
      caerulin-induced MKK3-TRAF3 association, downstream MKK3-p38 activation and 
      production of several pro-inflammatory cytokines (IL-1beta, TNF-alpha and IL-17). 
      Conversely, ectopic Rab21 overexpression in BMDMs potentiated caerulin-induced 
      MKK3-TRAF3 association and pro-inflammatory cytokines production. The 
      cytotoxicity of caerulin-activated BMDMs to co-cultured pancreatic acinar cells 
      was alleviated by Rab21 knockdown or knockout, but exacerbated with Rab21 
      overexpression. In vivo, administration of Rab21 shRNA lentivirus significantly 
      attenuated pancreatic and systemic inflammations in caerulin-injected AP mice. 
      Collectively, our results suggest that Rab21 mediates caerulin-induced MKK3-p38 
      activation and pro-inflammatory responses.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Wang, Na
AU  - Wang N
AD  - Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Meng, Wenying
AU  - Meng W
AD  - Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Jia, Rongrong
AU  - Jia R
AD  - Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China. Electronic address: 
      jiaronghh@163.com.
FAU - Xiang, Shihao
AU  - Xiang S
AD  - Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China. Electronic address: 
      drxiangshtj@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190808
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TNF Receptor-Associated Factor 3)
RN  - 888Y08971B (Ceruletide)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 3)
RN  - EC 3.6.1.- (rab21 protein, mouse)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - Acinar Cells/metabolism/pathology
MH  - Acute Disease
MH  - Animals
MH  - Cell Death
MH  - Ceruletide
MH  - Cytokines/metabolism
MH  - Enzyme Activation
MH  - Inflammation/metabolism/pathology
MH  - Inflammation Mediators/metabolism
MH  - MAP Kinase Kinase 3/*metabolism
MH  - Macrophages/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Pancreas/pathology
MH  - Pancreatitis/*metabolism/pathology
MH  - RNA, Small Interfering/metabolism
MH  - TNF Receptor-Associated Factor 3/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
MH  - rab GTP-Binding Proteins/*metabolism
OTO - NOTNLM
OT  - Acute pancreatitis
OT  - Caerulin
OT  - Pro-inflammatory response
OT  - Rab21
OT  - TRAF3-MKK3-p38 cascade
EDAT- 2019/08/14 06:00
MHDA- 2020/06/02 06:00
CRDT- 2019/08/13 06:00
PHST- 2019/07/25 00:00 [received]
PHST- 2019/08/02 00:00 [accepted]
PHST- 2019/08/14 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2019/08/13 06:00 [entrez]
AID - S0006-291X(19)31509-8 [pii]
AID - 10.1016/j.bbrc.2019.08.007 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Oct 8;518(1):50-58. doi: 
      10.1016/j.bbrc.2019.08.007. Epub 2019 Aug 8.