Mouse FK/CX3CL1(Fractalkine) ELISA Kit

Spinal metastasis occurs in 50-75% of bone metastases caused by hepatocellular carcinoma (HCC), and HCC-derived spinal metastasis can lead to a less favorable prognosis. Recently, several studies have demonstrated that C-X3-C motif chemokine ligand 1 (CX3CL1) is closely associated with cancer metastasis, and its secretion is modulated by a disintegrin and metalloproteinase 17 (ADAM17). Bone marrow endothelial cells (BMECs) are an essential component of bone marrow. However, little is known about the roles in and effects of BMECs on HCC spinal metastasis. The present study demonstrated that CX3CL1 and C-X-C motif chemokine receptor 3 (CXCR3) expression was upregulated in HCC spinal metastases, and that CX3CL1 promoted the migration and invasion of HCC cells to the spine. Western blot analysis revealed that the Src/protein tyrosine kinase 2 (PTK2) axis participated in CX3CL1-induced HCC cell invasion and migration. CX3CL1 also increased the expression of M2 macrophage markers in THP-1 monocytes. BMECs promoted the migration and invasion of Hep3B and MHCC97H cells by secreting soluble CX3CL1, whereas the neutralization of CX3CL1 inhibited this enhancement. CX3CL1 enhanced the activation of the phosphatidylinositol-4,5-bisphos-phate 3-kinase catalytic subunit alpha (PIK3CA)/AKT serine/threonine kinase 1 (AKT1) and Ras homolog family member A (RHOA)/Rho associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathways through the Src/PTK2 signaling pathway. Furthermore, ADAM17 was activated by mitogen-activated protein kinase (MAPK) z14 in BMECs and significantly promoted the secretion of CX3CL1. HCC cells enhanced the recruitment and proliferation of BMECs. The overexpression of CX3CR1 facilitated the spinal metastasis of HCC in a mouse modelin vivo. In addition,in vivoexperiments revealed that BMECs promoted the growth of HCC in the spine. The present study demonstrated that CX3CL1 participates in HCC spinal metastasis, and that BMECs play an important role in the regulation of CX3CL1 in the spinal metastatic environment.

During the pathogenesis of retinitis pigmentosa (RP), the roles of retinal microglial cells after activation have not been fully elucidated. Herein, experimental RP was induced in Sprague Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg, and the effects of MNU on the retinas were evaluated, respectively, by retinal histology and electroretinography recordings at serial time points. Time-dependent and gradual loss of photoreceptor cells, disrupted arrangement of the outer nuclear layer (ONL), and significant reductions in both a-wave and b-wave amplitudes were observed. Morphology changes were observed in retinal microglial cells; meanwhile, with time, the number of lba1-positive microglia and their infiltration into the ONL gradually increased. Furthermore, physical interaction of microglial-Muller cell processes following microglial activation was observed after MNU injection. In addition, Muller cells increased CX3CL1 secretion, enhanced microglial cell migration, and upregulated the CX3CR1 expression of the latter. Our observations implied that, during the pathogenesis of RP by MNU, microglial cells exhibit a prominent morphology change and Muller cells can induce activated microglia infiltration by increasing secretion of the chemotaxis factor, CX3CL1, and promoting the migration of retinal microglial cells. This novel finding highlights a potential therapeutic target aimed at regulating the microglial response.