The Chemokine Fractalkine Inhibits Fas-Mediated Cell Death of Brain Microglia
Abstract
Fractalkine is a CX3C-family chemokine, highly and constitutively expressed on the neuronal cell surface, for which a clear CNS physiological function has yet to be determined. Its cognate receptor, CX3CR-1, is constitutively expressed on microglia, the brain-resident macrophages; however, these cells do not express fractalkine. We now show that treatment of microglia with fractalkine maintains cell survival and inhibits Fas ligand-induced cell death in vitro. Biochemical characterization indicates that this occurs via mechanisms that may include 1) activation of the phosphatidylinositol-3 kinase/protein kinase B pathway, resulting in phosphorylation and blockade of the proapoptotic functions of BAD; 2) up-regulation of the antiapoptotic protein Bcl-xL; and 3) inhibition of the cleavage of BH3-interacting domain death agonist (BID). The observation that fractalkine serves as a survival factor for primary microglia in part by modulating the protein levels and the phosphorylation status of Bcl-2 family proteins reveals a novel physiological role for chemokines. These results, therefore, suggest that the interaction between fractalkine and CX3CR-1 may play an important role in promoting and preserving microglial cell survival in the CNS.
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CX3CR1 signaling inhibits microglial apoptosis via Fas-mediated mechanisms in vitro.
“Interestingly, CX3CR1 signaling inhibits microglial apoptosis via Fas-mediated mech- anisms in vitro.34”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [34]
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- Authors
- Boehme, S. A., Lio, F. M., Maciejewski-Lenoir, D., Bacon, K. B., & Conlon, P. J.
- Affiliations
- Neurocrine Biosciences (United States) (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-07-01
- Volume
- 165
- Issue
- 1
- Pages
- 397-403
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2132852509
- Cited by
- 192
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 5 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- fractalkine, CX3C chemokines, microglia, PI3K/Akt signaling, Bad phosphorylation, Bcl-xL, Bid cleavage, Bcl-2 family proteins, neuroprotection
- MeSH terms
- Animals, Brain, Carrier Proteins, Cell Communication, Cell Survival, Cells, Cultured, Enzyme Activation, Membrane Proteins, Phosphorylation, Proto-Oncogene Proteins, Cell Death, Rats, Sprague-Dawley, Apoptosis, Protein Serine-Threonine Kinases, Microglia, fas Receptor, Proto-Oncogene Proteins c-bcl-2, Chemokines, CXC, Chemokines, CX3C, bcl-Associated Death Protein, Proto-Oncogene Proteins c-akt, Rats, Chemokine CX3CL1
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