Disease relevance of Cx3cr1

• These findings suggest that fractalkine expression and CX3CR1-positive cell infiltration in diabetic kidneys might play an important role for progression of diabetic nephropathy [1].
• Differential expression of the chemokine receptors CX3CR1 and CCR1 by microglia and macrophages in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis [2].
• It binds to CX3C receptor 1 (CX3CR1), a pertussis toxin-sensitive G-protein-coupled receptor [3].
• In addition, a single injection of fractalkine receptor antagonist (neutralizing antibody against rat CX3C receptor-1; CX3CR1) delayed the development of mechanical allodynia and/or thermal hyperalgesia in two neuropathic pain models: chronic constriction injury (CCI) and sciatic inflammatory neuropathy [4].
• We mapped the regional and cellular localization of fractalkine and CX3CR1 in the rat spinal cord and dorsal root ganglion, under basal conditions and following induction of neuropathic pain, employing both an inflammatory (sciatic inflammatory neuropathy; SIN) as well as a traumatic (chronic constriction injury; CCI) model [5].

High impact information on Cx3cr1

• Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia [6].
• We undertook an extensive characterization of this chemokine and its receptor CX3CR1 in the brain to gain insights into use of chemokine-dependent systems in the central nervous system [6].
• These data describe mechanisms of cellular communication between neurons and microglia, involving fractalkine and CX3CR1, which occur in both normal and pathological states of the central nervous system [6].
• Induction of Fractalkine and CX3CR1 mediated by host CD8+ T cells in allograft tolerance induced by donor specific blood transfusion [7].
• RESULTS: We showed that the high CX3CR1 mRNA accumulation found in tolerated allografts was related to the active recruitment of monocytes/macrophages [7].

Biological context of Cx3cr1

• The RBS11 protein sequence is unusual in that it is without N-linked glycosylation consensus sequences in the putative exofacial regions [8].
• A series of cDNAs and a genomic clone (named RBS11) were isolated, from a variety of rat brainstem, pituitary and/or spinal cord cDNA libraries and a genomic library by low-stringency hybridization screening with a rat angiotensin receptor cDNA [8].
• CONCLUSIONS: Fractalkine and CX3CR1 upregulation were demonstrated in an early stage of diabetic kidney [1].
• The precise molecular basis for this phenotype is unclear, although differences in FKN binding, adhesive properties, and signaling efficiency between the CX3CR1 variants have been reported [9].
• TGF-beta1 increased steady state levels of CX3CR1 mRNA, 125I-fractalkine binding sites and blunted fractalkine-stimulated ERK1/2 phosphorylation [10].

Anatomical context of Cx3cr1

• Weak immunoreactivity for the CX3CL1 receptor, CX3CR1, was found in microglia in the spinal cord of either naïve rats or rats with inflammation [11].
• Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain [11].
• BACKGROUND: Fractalkine is induced on activated endothelial cells and promotes strong adhesion of T cells and monocytes via its receptor CX3CR1 [1].
• PERSPECTIVE: This study shows that spinal nerve injury, but not peripheral inflammation, induces the expression of a chemokine, CX3CL1 (fractalkine), in astrocytes and upregulates CX3CR1 in microglia in the spinal cord [11].
• Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions [5].

Associations of Cx3cr1 with chemical compounds

• Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys [1].
• INTRODUCTION: We sought to investigate whether there was a difference between cyclosporine (CsA) and mycophenolate mofetil (MMF) to affect the expression of Fractalkine/CX3CR1 in chronic allograft nephropathy (CAN) [12].
• Comparison of Cyclosporine Versus Mycophenolate Mofetil on Expression of Fractalkine and CX3CR1 in Chronic Allograft Nephropathy [12].
• Incubation of microglia with lipopolysaccharide (100 ng/ml) transiently suppressed expression of fractalkine receptor mRNA [13].

Physical interactions of Cx3cr1

• The half-life of CX3CR1 mRNA was unaltered by TGF-beta1 and two potential Smad binding elements (SBEs) were identified in the rat CX3CR1 promoter [10].

Regulatory relationships of Cx3cr1

• Taken together, our results demonstrate that TNF-alpha induces the expression of fractalkine and CX3CR1 in rat aortic SMCs and that this induction is mediated by NF-kappaB activation [3].
• TGF-beta1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia [10].

Other interactions of Cx3cr1

• Northern analysis indicates that the mRNA for RBS11 accumulates widely and unevenly in the adult rat, with the mRNA being most prominent in extracts of spinal cord, brain, kidney, gut, uterus and testes [8].
• Double immunofluorescence analysis showed co-localization of lectin, a marker for microglia with CX3CR1 but not with IL-1beta at 14 days following right vagotomy [14].
• Following peripheral nerve transection, CX3CR1 and TGF-beta1 are increased in a time-dependent manner within the injured facial motor nucleus [10].
• In HAPI cell cultures similar stimulation of mRNA levels was found for TNFalpha, MIP-1alpha, CXCR3, and CX3CR1 [15].

Analytical, diagnostic and therapeutic context of Cx3cr1

• Combined in situ hybridization and immunohistochemistry demonstrated intensely upregulated CCR1 mRNA expression in early, actively demyelinating plaques, whereas CX3CR1 displayed a more generalized expression pattern [2].
• Fractalkine also appears to modulate the effects of intrathecal morphine because coadministration of morphine with intrathecal neutralizing antibody against the fractalkine receptor (CX3CR1) potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia [16].
• The immunohistochemistry and quantitative real-time fluorescence polymerase chain reaction (PCR) were used to assess the distribution and expression of Fractalkine/CX3CR1 in the grafted kidney [12].
• The expression of Fractalkine/CX3CR1 in grafted kidneys at all the time points was significantly less in the MMF than in the CsA group or the control group (P < .05) [12].
• After facial motor nerve axotomy, dramatic changes in the levels of CX3CR1 and fractalkine in the facial nucleus were evident [6].

References