PMID- 30471852
OWN - NLM
STAT- MEDLINE
DCOM- 20190613
LR  - 20190613
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 508
IP  - 1
DP  - 2019 Jan 1
TI  - Requirement of Rab21 in LPS-induced TLR4 signaling and pro-inflammatory responses 
      in macrophages and monocytes.
PG  - 169-176
LID - S0006-291X(18)32489-6 [pii]
LID - 10.1016/j.bbrc.2018.11.074 [doi]
AB  - Lipopolysaccharide (LPS) induces macrophage/monocyte activation and 
      pro-inflammatory cytokines production by activating Toll-like receptor 4 (TLR-4) 
      signaling. Rab GTPase 21 (Rab21) is a member of the Rab GTPase subfamily. In the 
      present study, we show that LPS induced TLR4 and Rab21 association and endosomal 
      translocation in murine bone marrow-derived macrophages (BMDMs) and primary human 
      peripheral blood mononuclear cells (PBMCs). In BMDMs, shRNA-mediated stable 
      knockdown of Rab21 inhibited LPS-induced expression and production of 
      pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha). Conversely, forced 
      overexpression of Rab21 by an adenovirus construct potentiated LPS-induced IL-1beta, 
      IL-6 and TNF-alpha production in BMDMs. Further studies show that LPS-induced TLR4 
      endosomal traffic and downstream c-Jun and NFkappaB (nuclear factor-kappa B) 
      activation were significantly inhibited by Rab21 shRNA, but intensified with 
      Rab21 overexpression in BMDMs. Finally, in the primary human PBMCs, siRNA-induced 
      knockdown of Rab21 significantly inhibited LPS-induced IL-1beta, IL-6 and TNF-alpha 
      production. Taken together, we suggest that Rab21 regulates LPS-induced 
      pro-inflammatory responses by promoting TLR4 endosomal traffic and downstream 
      signaling activation.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Li, Ping
AU  - Li P
AD  - Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, China.
FAU - Wu, Yong-Hong
AU  - Wu YH
AD  - Lab of Clinical Immunology and Pathogen Detection, Xi'an Medical University, 
      Xi'an, China.
FAU - Zhu, Yan-Ting
AU  - Zhu YT
AD  - Department of Respiration, The First Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, China.
FAU - Li, Man-Xiang
AU  - Li MX
AD  - Department of Respiration, The First Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, China. Electronic address: limanxiangxa@163.com.
FAU - Pei, Hong-Hong
AU  - Pei HH
AD  - Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, China. Electronic address: drpeihonghong@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181122
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 3.6.1.- (rab21 protein, mouse)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Lipopolysaccharides/antagonists & inhibitors/*pharmacology
MH  - Macrophages/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/*drug effects/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptor 4/antagonists & inhibitors/*metabolism
MH  - rab GTP-Binding Proteins/antagonists & inhibitors/genetics/*metabolism
OTO - NOTNLM
OT  - Cytokines
OT  - LPS
OT  - Rab21
OT  - Signaling
OT  - TLR4
EDAT- 2018/11/26 06:00
MHDA- 2019/06/14 06:00
CRDT- 2018/11/26 06:00
PHST- 2018/11/02 00:00 [received]
PHST- 2018/11/12 00:00 [accepted]
PHST- 2018/11/26 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/11/26 06:00 [entrez]
AID - S0006-291X(18)32489-6 [pii]
AID - 10.1016/j.bbrc.2018.11.074 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Jan 1;508(1):169-176. doi: 
      10.1016/j.bbrc.2018.11.074. Epub 2018 Nov 22.