Journal article
CXCL12-induced cleavage of CX3CL1: potential role in neuroprotection
Journal of neurovirology, Vol.13, pp.85-85
01 Jan 2007
Abstract
Chemokines are involved in various physiological and pathological processes in the CNS, including neuroinnammation/neuroAIDS. CX3CL1 (Fractalkine) and CXCL12 (SDF-1) are two chemokines that are constitutively expressed in the brain. CX3CL1 can exist as a transmembrane protein, which acts as adhesive molecule, or can be cleaved by ADAMs (A Disintegrin and Metalloproteinase) and act as a soluble protein. Both soluble and membrane-attached CX3CL1 interact with the specific CX3CL1 receptor, CX3CR1. In vitro and in vivo studies suggest that CX3CL1 and CXCL12 may have neuroprotective effects, though the mechanisms involved are not completely clear. The aim of this study was to establish whether neuronal production of CX3CL1 is regulated by CXCL12, and determine whether this regulation is involved in neuronal protection. Through the use of a pathway-specific DNA microarray, RT-PCR, and qRT-PCR, we show that the gene for CX3CL1 is up-regulated in neurons treated with CXCL12 (20nM, 18hr). Furthermore, treatment with CXCL12 stimulates cleavage of CX3CL1. Addition of different metalloproteinase inhibitors abolishes CXCL12-induced cleavage. We also found that treatment of neuronal cultures with NMDA can affect levels of soluble/cellular CX3CL1 in a time-dependent manner. This is important as we and others have previously shown that both CXCL12 and CX3CL1 can protect neurons from exitotoxicity. Survival assays will test the hypothesis that soluble CX3CL1 contributes to the action of CXCL12 on neuronal survival. Our findings so far uncover a novel interaction between the two chemokines, which may play an important role in the regulation of their individual functions in the brain.
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Details
- Title
- CXCL12-induced cleavage of CX3CL1: potential role in neuroprotection
- Creators
- R HippensteelS ShimizuO Meucci
- Publication Details
- Journal of neurovirology, Vol.13, pp.85-85
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Identifiers
- 991019170454204721