PMID- 24628787
OWN - NLM
STAT- MEDLINE
DCOM- 20140514
LR  - 20211021
IS  - 1365-2613 (Electronic)
IS  - 0959-9673 (Print)
IS  - 0959-9673 (Linking)
VI  - 95
IP  - 2
DP  - 2014 Apr
TI  - CX3CR1 RNAi inhibits hypoxia-induced microglia activation via p38MAPK/PKC 
      pathway.
PG  - 153-7
LID - 10.1111/iep.12065 [doi]
AB  - There is accumulating evidence which demonstrates that chronic cerebral ischaemia 
      can induce white matter lesions (WMLs), and microglia-activation-mediated 
      cytokines and proteases releasing during the ischaemia might play a vital role in 
      pathogenesis. In addition, hypoxia-induced upregulated expression of fractalkine 
      promotes the activation of microglia and their migration to the lesions through 
      interaction with its receptor CX3CR1. However, the specific mechanisms involved 
      in fractalkine/CX3CR1-mediated microglial activation have not been fully 
      identified. In the present study, we constructed lentivirus encoding shRNA 
      against CX3CR1 and transduced into microglial cells in under hypoxic conditions. 
      Moreover, we analysed the proliferation, cytokine secretion and signal-pathway 
      activation of the microglia. We found that CX3CR1 RNAi-mediated gene 
      downregulation could attenuate hypoxic-induced microglial proliferation, cytokine 
      secretion [including tumuor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)] 
      and matrix metalloproteinase-2 (MMP-2) synthesis. These effects were shown to be 
      nediated through p38MAPK/PKC activation. Therefore, our results reveal a novel 
      mechanism of fractalkine/CX3CR1 involvement in activation of microglia. Thus 
      CX3CR1 RNAi might provide a therapeutic strategy which could be useful in chronic 
      cerebral ischaemia.
CI  - (c) 2014 The Authors. International Journal of Experimental Pathology (c) 2014 
      International Journal of Experimental Pathology.
FAU - Liu, Yong
AU  - Liu Y
AD  - Department of Neurology, Xinqiao Hospital, Third Military Medical University, 
      Chongqing, China.
FAU - Zhao, Tianzhi
AU  - Zhao T
FAU - Yang, Zhao
AU  - Yang Z
FAU - Li, Qianning
AU  - Li Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Exp Pathol
JT  - International journal of experimental pathology
JID - 9014042
RN  - 0 (CX3C Chemokine Receptor 1)
RN  - 0 (Chemokine CX3CL1)
RN  - 0 (Cx3cr1 protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - CX3C Chemokine Receptor 1
MH  - Cell Hypoxia/*physiology
MH  - Cell Line
MH  - Cell Proliferation
MH  - Chemokine CX3CL1/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Mice
MH  - Microglia/*metabolism
MH  - Protein Kinase C/*metabolism
MH  - RNA Interference
MH  - Receptors, Chemokine/genetics/*metabolism
MH  - Signal Transduction/*physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC3960043
OTO - NOTNLM
OT  - CX3CR1
OT  - RNAi
OT  - hypoxi
OT  - microglia
OT  - p38MAPK/PKC
EDAT- 2014/03/19 06:00
MHDA- 2014/05/16 06:00
PMCR- 2015/04/01
CRDT- 2014/03/18 06:00
PHST- 2013/09/12 00:00 [received]
PHST- 2013/11/16 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - 10.1111/iep.12065 [doi]
PST - ppublish
SO  - Int J Exp Pathol. 2014 Apr;95(2):153-7. doi: 10.1111/iep.12065.