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CX3CL1/CX3CR1-Mediated Microglia Activation Plays a Detrimental Role in Ischemic Mice Brain via p38MAPK/PKC Pathway
Abstract
The exact roles of activated microglia and fractalkine (CX3CL1)/fractalkine receptor (CX3CR1) signaling are not fully understood in brain ischemic injury and the findings reported are controversial. Here, we investigated the effects of CX3CR1 siRNA on the expression of CX3CR1, p38 mitogen-activated protein kinase (p38MAPK), Protein Kinase C (PKC) and inflammatory cytokines, microglia activation, white matter lesions, and cognitive function in mice treated with bilateral common carotid artery stenosis (BCAS) in vivo as well as effects of exogenous CX3CL1, CX3CR1 siRNA, and SB2035080 on expression of inflammatory cytokines in BV2 microglia treated with oxygen–glucose deprivation (OGD) in vitro. We showed that CX3CR1 siRNA significantly inhibited the increased expression of CX3CR1, p38MAPK, PKC as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and also attenuated microglia activation, white matter lesions, and cognitive deficits induced by BCAS in mice brain. We also showed that exogenous CX3CL1 could induce a further enhancement in TNF-α and IL-1β expression, which could be suppressed by CX3CR1 siRNA or by the p38MAPK inhibitor in OGD-treated BV2 microglial cells in vitro. Our findings indicated that CX3CL1/CX3CR1-mediated microglial activation plays a detrimental role in ischemic brain via p38MAPK/PKC signaling and also suggested that CX3CL1/CX3CR1 axis might be a putative therapeutic target to disrupt the cascade of deleterious events that lead to brain ischemic injury.
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“many studies have confirmed that the CX3CL1/CX3CR1 axis plays an important role in regulating microglial activation and neuroinflammation [26, 27].”
From CX3CL1/CX3CR1 axis attenuates early brain injury via promoting the delivery of exosomal microRNA-124 from neuron to microglia after subarachnoid hemorrhage (2020) · cites this paper as [27]
Citations
Cites
A new class of membrane-bound chemokine with a CX3C motif
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Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury
Soriano, S. G., Amaravadi, L. S., Wang, Y. F., Zhou, H., Yu, G. X., Tonra, J. R., Fairchild-Huntress, V., Fang, Q., Dunmore, J. H., Huszar, D., et al. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00033-4 · Cited by 222
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Cited by
Sorted by citations
Tissue-specific Role of CX3CR1 Expressing Immune Cells and Their Relationships with Human Disease
Lee, M., Lee, Y., Song, J., Lee, J., & Chang, S.-Y. (2018) · Immune Network · doi:10.4110/in.2018.18.e5 · Cited by 260
“However, inhibiting CX3CR1 expression by siRNA can decrease TNF-α and IL-1β cytokine production in a different ischemic animal model (50).”
BackgroundChen, X., Jiang, M., Li, H., Wang, Y., Shen, H., Li, X., Zhang, Y., Wu, J., Yu, Z., & Chen, G. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01882-6 · Cited by 85
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“Depending on the disorder or the course of brain injury, CX3CL1 contributes to augment microglia pro-inflammatory response or maintain microglia in quiescence (Liu et al., 2015; Zanier et al., 2016; Dorfman et al., 2017).”
Background
Metadata
- Authors
- Liu, Y., Wu, X.-M., Luo, Q.-Q., Huang, S., Yang, Q.-W. Q., Wang, F.-X., Ke, Y., & Qian, Z.-M.
- Affiliations
- Department of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China
- Department of Neurobiology, Institute for Nautical Medicine, Nantong University, Nantong, China
- Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Pu Dong, Shanghai, China
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong, China
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2015-05-13
- Volume
- 35
- Issue
- 10
- Pages
- 1623-1631
- ISSN
- 0271-678X
- 1559-7016
- Cited by
- 84
- References
- 5
- Language
- en
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- CoChat. (2026). Citation check: CX3CL1/CX3CR1-Mediated Microglia Activation Plays a Detrimental Role in Ischemic Mice Brain via p38MAPK/PKC Pathway. https://app.cochat.ai/papers/10.1038/jcbfm.2015.97
- The paper
- Liu, Y., Wu, X.-M., Luo, Q.-Q., Huang, S., Yang, Q.-W. Q., Wang, F.-X., Ke, Y., & Qian, Z.-M. (2015). CX3CL1/CX3CR1-Mediated Microglia Activation Plays a Detrimental Role in Ischemic Mice Brain via p38MAPK/PKC Pathway. Journal of Cerebral Blood Flow & Metabolism. https://doi.org/10.1038/jcbfm.2015.97
