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CX 3 CR 1 RNA i inhibits hypoxia‐induced microglia activation via p38 MAPK / PKC pathway
Author(s) -
Liu Yong,
Zhao Tianzhi,
Yang Zhao,
Li Qianning
Publication year - 2014
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12065
Subject(s) - microglia , cx3cr1 , microbiology and biotechnology , downregulation and upregulation , cytokine , mapk/erk pathway , proinflammatory cytokine , tumor necrosis factor alpha , chemistry , chemokine , signal transduction , biology , inflammation , immunology , biochemistry , chemokine receptor , gene
Summary There is accumulating evidence which demonstrates that chronic cerebral ischaemia can induce white matter lesions ( WML s), 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 CX 3 CR 1. However, the specific mechanisms involved in fractalkine/ CX 3 CR 1‐mediated microglial activation have not been fully identified. In the present study, we constructed lentivirus encoding sh RNA against CX 3 CR 1 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 CX 3 CR 1 RNA i‐mediated gene downregulation could attenuate hypoxic‐induced microglial proliferation, cytokine secretion [including tumuor necrosis factor‐α ( TNF ‐α), interleukin‐1β ( IL ‐1β)] and matrix metalloproteinase‐2 ( MMP ‐2) synthesis. These effects were shown to be nediated through p38 MAPK / PKC activation. Therefore, our results reveal a novel mechanism of fractalkine/ CX 3 CR 1 involvement in activation of microglia. Thus CX 3 CR 1 RNA i might provide a therapeutic strategy which could be useful in chronic cerebral ischaemia.