Clinical significance of expression level of CX3CL1-CX3CR1 axis in bone metastasis of lung cancer.

PURPOSE: To investigate the clinical significance of CX3 chemokine ligand 1(CX3CL1) and CX3CR1 in patients with bone metastasis from lung cancer. The expression levels of CX3CL1 and CX3CR1 mRNA and protein in primary lung cancer and lung cancer bone metastasis were detected by qRT-PCR and Western blot. METHODS: One hundred patients with lung cancer were divided into a boneless metastasis group (50 patients with bone metastasis) and a bone metastasis group (50 patients without distant metastasis). The bone transfer component was graded by Soloway classification (0 to III). The expression levels of serum CX3CL1-CX3CR1 axis were detected by enzyme-linked immunosorbent assay (ELISA). RT-qPCR and Western Blot were used to verify the transfection efficiency. The scratching assay was used to detect the migration of CX3CL1 to 95-D cells after down-regulating the expression of CX3CR1. RESULTS: The expression levels of CX3CL1 and CX3CR1 mRNA and protein in the primary lung cancer and lung cancer bone metastasis were significantly higher than those in the adjacent tissues (P < 0.0001). The levels of serum CX3CL1 and CX3CR1 in bone metastasis group were significantly higher than those in boneless metastasis group and healthy control group (P < 0.05). In the bone metastasis group, the levels of serum CX3CL1 and CX3CR1 were significantly positively correlated with the degree of disease progression (P < 0.01). CONCLUSION: The expression level of serum CX3CL1-CX3CR1 axis is expected to be an auxiliary reference index for monitoring bone metastasis of lung cancer.

Renovascular hypertension increases serum TNF and CX3CL1 in experimental Trypanosoma cruzi infection.

Trypanosoma cruzi triggers a progressive inflammatory response affecting cardiovascular functions in humans and experimental models. Angiotensin II, a key effector of the renin-angiotensin system, plays roles in mediating hypertension, heart failure, and inflammatory responses. T. cruzi and AngII can induce inflammatory responses by releasing inflammatory mediators. The aim of this study was to evaluate systemic AngII, tumor necrosis factor (TNF), and CX3CL1 mediators in a two-kidney one-clip (2K1C) renovascular hypertension model using Wistar rats infected with T. cruzi. Our data showed an increase in serum AngII in uninfected and T. cruzi-infected rats 1 week after 2K1C surgery compared to non-2K1C (Sham) animals. The baseline systolic blood pressure was higher in both uninfected and infected 2K1C rats. Despite no difference in circulating parasites in the acute phase of infection, elevated serum TNF and CX3CL1 were observed at 8 weeks post-infection in 2K1C rats in association with higher cardiac inflammatory infiltration. In summary, AngII-induced hypertension associated with T. cruzi infection may act synergistically to increase TNF and CX3CL1 in the 2K1C rat model, thereby intensifying cardiac inflammatory infiltration and worsening the underlying inflammation triggered by this protozoan.

Renovascular hypertension increases serum TNF and CX3CL1 in experimental Trypanosoma cruzi infection

Trypanosoma cruzi triggers a progressive inflammatory response affecting cardiovascular functions in humans and experimental models. Angiotensin II, a key effector of the renin-angiotensin system, plays roles in mediating hypertension, heart failure, and inflammatory responses. T. cruzi and AngII can induce inflammatory responses by releasing inflammatory mediators. The aim of this study was to evaluate systemic AngII, tumor necrosis factor (TNF), and CX3CL1 mediators in a two-kidney one-clip (2K1C) renovascular hypertension model using Wistar rats infected with T. cruzi. Our data showed an increase in serum AngII in uninfected and T. cruzi-infected rats 1 week after 2K1C surgery compared to non-2K1C (Sham) animals. The baseline systolic blood pressure was higher in both uninfected and infected 2K1C rats. Despite no difference in circulating parasites in the acute phase of infection, elevated serum TNF and CX3CL1 were observed at 8 weeks post-infection in 2K1C rats in association with higher cardiac inflammatory infiltration. In summary, AngII-induced hypertension associated with T. cruzi infection may act synergistically to increase TNF and CX3CL1 in the 2K1C rat model, thereby intensifying cardiac inflammatory infiltration and worsening the underlying inflammation triggered by this protozoan.

Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism.

Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

Soluble fractalkine in the plasma of fibromyalgia patients.

Fibromyalgia is a form of non-articular rheumatism in which inflammatory cytokines seem to be involved. However, there is still no analytical specific diagnostic criterion for this disease. The aim was to examine a possible role of fractalkine as a biomarker in fibromyalgia. Plasma levels of soluble fractalkine were compared between women diagnosed with fibromyalgia (n=17) and healthy women (n=10) as controls. Fractalkine released by monocytes was also evaluated. Fibromyalgia patients showed lower plasma fractalkine than healthy women. Since most inflammatory pathologies show elevated plasma levels of soluble fractalkine, the results may contribute towards a differential diagnosis for fibromyalgia.

Protein deficiency alters CX3CL1 and endothelin-1 in experimental Trypanosoma cruzi-induced cardiomyopathy.

OBJECTIVE: Chagas heart disease is developed as a result of the infection with Trypanosoma cruzi. Protein malnutrition contributes to secondary immunodeficiency. The aim of this study was to investigate the role of a low protein diet on the production of endothelin-1 and CX3CL1 in blood and cardiac tissue samples in an experimental model with T. cruzi infection. METHODS: Fisher rats were submitted to low protein (6%) and normal protein (15%) diets and then infected with the Y strain of T. cruzi. At days 15 and 120, parasites and immune cells were evaluated. RESULTS: The low protein diet reduced body weight and circulating serum proteins, but promoted elevation of CX3CL1 and endothelin-1 levels in infected animals, which were unable to control blood parasitemia replication. In heart tissue, the low protein diet reduced cardiac CX3CL1, endothelin-1 and leucocyte infiltration in the acute phase, in particular CD68 and CD163 macrophage phenotypes. CONCLUSION: Together, these results highlight the participation of endothelin-1 and CX3CL1 in the inflammatory process of Chagas diesease, both being mediators partially controlled by the host nutritional status.