Disease relevance of Cx3cl1

• To determine whether FK is critically involved in atherogenesis, we deleted the gene for CX(3)CR1 and crossed these mice into the apoE(-/-) background [1].
• CONCLUSIONS: This study has identified a role for CX(3)CR1 in the normal recruitment of MHC class II(+) putative DCs into the corneal epithelium and establishes a model for investigating monocyte-derived cells and fractalkine/CX(3)CR1 interactions during corneal disease [2].
• We therefore undertook this study to investigate whether Fkn antagonist inhibits the initiation and progression of lupus nephritis in MRL/lpr mice [3].
• CONCLUSION: We prepared a novel potent Fkn antagonist and demonstrated its ability to delay the initiation and ameliorate the progression of lupus nephritis [3].
• In contrast, Fkn antagonist did not affect pneumonitis, sialadenitis, lymphadenopathy, or splenomegaly [3].
• We showed for the first time the immunologic mechanisms by which targeted IL-2 treatment of neuroblastoma with an FKN-rich microenvironment induces an effective antitumor response [4].

High impact information on Cx3cl1

• We report here CX3C chemokine mimicry for the G glycoprotein of respiratory syncytial virus (RSV) and show binding to CX3CR1--the specific receptor for the CX3C chemokine fractalkine--and induction of leukocyte chemotaxis [5].
• CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein [5].
• Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C [5].
• Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine in atherogenesis [1].
• Fractalkine (FK) is a structurally unusual chemokine that can act either as a soluble chemotactic factor or as a transmembrane-anchored adhesion receptor for circulating leukocytes [1].

Chemical compound and disease context of Cx3cl1

• The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P [6].

Biological context of Cx3cl1

• Using the Cx3cl1 promoter as an example of a target gene, we demonstrated direct binding of RFX4_v3 to the Cx3cl1 promoter, and trans-acting activity of RFX4_v3 protein to stimulate gene expression [7].
• Despite their clinical relevance, the mechanisms underlying monocyte/macrophage chemotaxis to CX3CL1 remain poorly documented [8].
• In several pathologies, excessive production of CX3CL1 at specific sites leads primarily to monocyte/macrophage recruitment, which causes tissue and vascular damage [8].
• CX3CL1 also triggers tyrosine phosphorylation of proteins localized in those protrusions [8].
• These expression profiles indicate that tissue specificity of Scya17 is precisely regulated by two independent mechanisms, one by transcription from its own promoter and the other from the promoter of Scyd1 followed by tissue-specific alternative splicing [9].

Anatomical context of Cx3cl1

• Here we report that FK is robustly expressed in lesional smooth muscle cells, but not macrophages, in apoE(-/-) mice on a high-fat diet [1].
• A polymorphism in the FK receptor, CX(3)CR1, has been linked to a decrease in the incidence of coronary artery disease [1].
• CX3CL1 (fractalkine), the only member of the delta subclass of chemokines, is a known chemotactic factor for monocytes/macrophages as well as NK cells and T lymphocytes [8].
• Using the murine monocyte/macrophage RAW cell line, we show that CX3CL1 treatment elicits a rapid and transient increase in F-actin and the formation of F-actin-enriched cell protrusions [8].
• These data suggest that in monocytes/macrophages, Syk is essential for proper reorganization of the actin cytoskeleton in response to CX3CL1 and is therefore required for cell chemotaxis to CX3CL1 [8].

Associations of Cx3cl1 with chemical compounds

• Acute inflammatory responses in the CNS, induced by stereotaxic injections of lipopolysaccharide or kainic acid, results in activation of microglia and astrocytes but no detectable changes in the glial expression of CX3CL1 or CX3CR1 [10].
• Neither the production of fractalkine nor its receptor expression was up-regulated by lipopolysaccharide (LPS), as measured by mRNA expression and protein synthesis [11].
• This cytokine- and growth factor-stimulated CX3CL1/fractalkine expression could be abolished by the nuclear factor-kappaB inhibitors, curcumin and MG132 [12].

Regulatory relationships of Cx3cl1

• RESULTS: Fkn analogs truncated by >/=4 amino acid residues from the N-terminus failed to induce chemotaxis and calcium influx by CX3CR1-expressing cells [3].

Other interactions of Cx3cl1

• Cells with reduced Syk expression also exhibit a major defect in CX3CL1-induced cytoskeletal remodeling [8].
• In a prion model of chronic neurodegeneration and inflammation, CX3CL1 immunoreactivity is upregulated in astrocytes and CX3CR1 expression is elevated on microglia [10].
• To determine the capacity of FKN on endothelial cells to promote leukocyte adhesion, we performed adhesion assays with PBMC and monolayers of TNF-alpha-activated murine endothelial cells under low-shear conditions [13].
• The results indicated a high level of fractalkine protein in cortex, hippocampus, basal ganglia, and olfactory bulb [14].

Analytical, diagnostic and therapeutic context of Cx3cl1

• Inhibition of fractalkine ameliorates murine collagen-induced arthritis [15].
• Immunohistochemistry was performed using primary antibodies recognizing soluble and membrane-bound CX3CL1 and the N-terminus of the CX3CR1 [10].
• To determine the functional significance of FKN in rejection, we treated cardiac allograft recipients with daily injections of anti-CX(3)CR1 Ab [13].
• Gene expression study results, obtained by both semiquantitative PCR and in situ hybridization, matched protein localization with the highest levels of fractalkine transcript detected in the hippocampus, cortex, and striatum [14].
• Regulation of CX3CL1/fractalkine expression in cultured MCs was determined by northern and western blot analysis [12].

References