Fractalkine inhibits lipopolysaccharide-induced M1 polarization of macrophages by activating Wnt/β-catenin signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which fractalkine (CX3CL1; FKN) inhibits lipopolysaccharide (LPS)-induced immunological response in RAW264.7 cells.@*METHODS@#A RAW264.7 cell model overexpressing FKN was established by transfection with the lentiviral vector CX3CL1. The effects of LPS, ICG-001 (a Wnt/β-catenin signaling pathway inhibitor), either alone or in combination, on M1 polarization of na?ve and FKN-overexpressing RAW264.7 cells were evaluated by detecting of intereukin-6 (IL-6) and tumor necrosis factor-α (TNF-@*RESULTS@#The RAW264.7 cell model of FKN overexpression was successfully established. In na?ve RAW264.7 cells, treatment with both ICG-001 and LPS, as compared with LPS alone, significant promoted TNF-@*CONCLUSIONS@#FKN overexpression suppresses LPS-induced M1 type polarization of RAW264.7 cells by activating Wnt/β-catenin signaling pathway.

Progress of CX3CL1 (Fractalkine) and its receptor CX3CR1 in regulating central nervous system disease / 医学研究生学报

In recent years, researches constituted to show that the occurrence of central nervous system diseases such as Parkinson′s disease, Alzheimer′s disease and multiple sclerosis may have association with the inflammation of central nervous system. The chemokine CX3CL1 is mainly produced by neurons and acts on the central nervous system. After binding to the receptor CX3CR1, by inhibiting the calcium influx induced by NMDA in neurons, it can promote the activation of protein kinase and activate nuclear transcription factor kappa B, reduce the release of inflammatory factors, and stabilize the status of microglia, thus suppress the inflammatory response of the central nervous system and reduce neuronal death, which play a certain role in neuroprotective effect. Therefore, the interaction between CX3CL1 and CX3CR1 is expected to be a new target in the treatment of central nervous system diseases. In this paper, the structure of CX3CL1 and its receptor CX3CR1, the interaction of signal axis and their research progress on central nervous system diseases are reviewed.

Effects of chemokine fractalkine and m2 macrophages on biological functions of pancreatic cancer cell line / 肿瘤

Objective: To investigate the effects of cytokine Fractalkine (FKN) combined with M2-type macrophages on the proliferation, invasion, and migration of human pancreatic cancer PANC-1 cells. Methods: The recombinant lentivirus HBLV-h-FKN-GFP-PURO carrying FKN gene was constructed and infected into PANC-1 cells. THP-1 cells, a kind of monocytes of human leukemia, were induced into M2-type macrophages by phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4) in suquence. Then the non-contacting co-culture model of pancreatic cancer cells and M2-type macrophages with different expression level of FKN was established by Transwell chamber system. The proliferation, invasion and migration of human pancreatic cancer PANC-1 cells were detected by CCK-8 method, Transwell chamber test and wound-healing assay, respectievely. Results: As compared with the uninfected control and empty lentivirus infected groups, the expression level of FKN protein was significantly increased in human pancreatic cancer PANC-1 cells infected with recombinant lentivirus HBLV-h-FKN-GFP-PURO (both P < 0.001). THP-1 cells were successively induced to become M2-type macrophages with high expression of arginase-1 (Arg-1) and low expression of inducible nitric oxide synthase (iNOS) protein (PArg-1 < 0.001, PiNOS < 0.01). The recruiting ability of PANC-1 cells to M2 type macrophages was enhanced after FKN over-expression (P < 0.001). The proliferation, invasion and migration abilities of PANC-1 cells were increased after FKN over-expression (all P < 0.001), and were more significantly increased after co-culture with M2-type macrophages (all P < 0.01). There were interactions between M2-type macrophages and FKN for proliferation, invasion and migration abilities of PANC-1 cells (P < 0.01, P < 0.01, P < 0.05). Conclusion: The chemokine FKN promotes the recruitment of PANC-1 cells to M2-type macrophages. Both FKN and M2-type macrophages can enhance the proliferation, invasion and migration abilities of PANC-1 cells, and there is synergistical interaction between them.

Effects of curcumin on pro-inflammatory factors in pulmonary microvascular endothelial cell thrombus model stimulated by thrombus / 中国中西医结合急救杂志

Objective To explore the effects of curcumin on pro-inflammatory factors in the lung microvascular endothelial cells (LMVEC) model stimulated by thrombus. Methods The LMVECs were divided into six groups according to the random number table method. No treatment was given to the blank control group ; the model group was cultured for 7 hours in normal medium; the curcumin group was treated with 40 μmol/L curcumin for 72 hours ; the shRNA group was infected with shRNA adenovirus for 72 hours; the irregular chemokines (CX3CL1) overexpression group was infected with CX3CL1 overexpressing adenovirus for 72 hours; the shRNA+curcumin group infected with shRNA adenovirus and treated with 40 μmol/L curcumin together for 72 hours; CX3CL1 overexpression +curcumin group infected with CX3CL1 overexpressing adenovirus and treated with 40 μmol/L curcumin together for 72 hours. After each group was given the corresponding pretreatment, the thrombus natural precipitation was added each group for 12 hours. The contents of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the mRNA expression levels of CX3CL1, CX3CL1 receptor (CX3CR1), IL-6, TNF-α and the protein expression levels of CX3CL1/CX3CR1, CX3CR1/NF-κB in various groups were observed, repeat 3 times in each group. Results The contents and mRNA expression of IL-6, TNF-αand protein expression of CX3CR1, NF-κB in the LMVEC group were significantly higher than those in blank control group [IL-6 (ng/L): 207.90±16.69 vs. 85.93±20.32, TNF-α (ng/L): 239.60±15.27 vs. 101.23±11.92; IL-6 mRNA: 0.66±0.05 vs. 0.11±0.02, TNF-α mRNA: 1.06±0.04 vs. 0.02±0.01; CX3CR1 protein:3.94±0.58 vs. 1.00±0.31, NF-κB protein: 1.20±0.07 vs. 1.00±0.10; all P < 0.05]; the contents of IL-6 in shRNA group, CX3CL1 overexpression group, shRNA + curcumin group, CX3CL1 overexpression + curcumin group were all obviously lower than those in LMVEC group (ng/L: 183.60±11.52, 159.27±15.02, 117.03±7.91, 119.97±11.43 vs. 207.90±16.69, all P < 0.01); the content of TNF-α was markedly increased in shRNA group compared with that of LMVEC group (ng/L: 282.00±5.63 vs. 239.6±15.27), while the contents of TNF-α in CX3CL1 overexpression group, shRNA+ curcumin group, CX3CL1 overexpression + curcumin group were all lower than those in LMVEC group (ng/L: 216.97±9.20, 203.97±19.03, 191.97±17.50 vs. 239.6±15.27, all P < 0.05). The mRNA expression levels in CX3CL1 overexpression group and CX3CL1 overexpression + curcumin group were significantly higher than those in the blank control group and the LMVEC group (CX3CL1 mRNA: 55 210.3±1 209.2, 165 296.3±8 082.4 vs. 3.3±0.6, 2.0±0.0, all P < 0.01). The mRNA expression level of IL-6 in shRNA group was higher than that in LMVEC group (0.82±0.17 vs. 0.66±0.05), the mRNA expression level of IL-6 in CX3CL1 overexpression was lower than that in LMVEC group (0.29±0.03 vs. 0.66±0.05), the changes after pretreatment with curcumin were more significant (1.06±0.03 vs. 0.66±0.05 and 0.15±0.01 vs. 0.66±0.05); the mRNA expressions of TNF-α in shRNA group, CX3CL1 overexpression group, shRNA+ curcumin group were significantly lower than those in LMVEC group (0.41±0.04, 0.88±0.07, 1.01±0.02 vs. 1.06±0.04), the mRNA expression level of TNF-α in CX3CL1 overexpression + curcumin group was significantly higher than that in LMVEC group (1.36±0.01 vs. 1.06±0.04). The protein expression of CX3CL1, CX3CR1, NF-κB in shRNA group, CX3CL1 overexpression group, shRNA + curcumin group, CX3CL1 overexpressing + curcumin group were significantly higher than those in the LMVEC group (CX3CL1 protein: 0.41±0.07, 0.59±0.09, 0.69±0.61, 1.02±0.23 vs. 1.33±0.33, CX3CR1 protein: 0.85±0.18, 1.10±0.16, 1.32±0.18, 1.54±0.08 vs. 3.94±0.58, NF-κB protein: 0.33±0.07, 0.41±0.08, 0.41±0.07, 0.63±0.08 vs. 1.20±0.07). Conclusion Curcumin can inhibit the secretion of IL-6, TNF-α, CX3CR1 and NF-κB in thrombus-stimulated LMVEC model.

Association between serum Fractalkine and obesity and type 2 diabetic mellitus / 中国糖尿病杂志

Objective To investigate the association between serum chemotactic factor fractalkine (FKN) level and obesity and type 2 diabetic mellitus (T2DM).Methods According to BMI,88 cases of healthy persons with normal glucose tolerance (NGT) were divided into normal weight group (A group,n =44,BMI＜ 24 kg/m2) and obesity group (B group,n =44,BMI≥ 24 kg/m2);88 cases of newly diagnosed T2DM patients (T2DM group) were divided into the normal weight group (C group,n=44,BMI＜24 kg/m2) and obesity group (D group,n=44,BMI≥24 kg/m2).FKN and TNF-α levels were measured by ELISA.Results Serum FKN in T2DM group (0.625± 0.090) ng/ml was higher than that in NGT group (0.395±0.110) ng/ml (P＜0.01).The levels of FKN in C group (0.55±0.08) ng/ml were higher than that of A group (0.34±0.14) ng/ml and B group (0.45±0.08) ng/ml P＜0.01).Serum FKN was positively correlated with and the levels of FPG,HbA1 c,WHR,BMI,C reactive protein (C-RP),HOMA-IR and TNF-α (r=0.578,0.592,0.616,0.596,0.909,0.872 and 0.827,P＜0.01) in T2DM group.FKN was negatively correlated with HDL-C (r =-0.216,P ＜ 0.05).Multivariate regression analysis showed that C-RP,BMI and TNF-α were independent factors related to FKN (β=0.441,0.158 and 0.221,P＜0.05).Conclusion Serum FKN is closely related to inflammation response in T2DM patients.FKN may play an important role in the pathogenesis and development of T2DM and obesity.

Effects of chemokine Fractalkine on proliferation and invasion of human pancreatic cancer cell lines by regulating IL-6/STAT3 signal pathway / 重庆医学

Objective To explore the effects of chemokine Fractalkine(FKN) on the proliferation and invasion of human pancreatic cancer cell lines PANC-1 and SW-1990 by regulating IL-6/STAT3 signal pathway.Methods Adenovirus served as the vector to construct and synthesizing FKN-small interfering RNA(siRNA),then which was transfected into PANC-1 and SW-1990.The proliferation and invasion ability of cells was determined by CCK-8 assay and Transwell assay.Expression of FKN,IL-6 and STAT3 protein and mRNA was detected by Western blot and RT-qPCR.Results After transfecting FKN-siRNA for 24 h,the absorbance values(A value) in the PANC-1 and SW-1990 groups had no significant changes,the A value at 48,72 h in the FKN-siRNA group was significantly higher than that in the control group and FKN-siRNA negative group (P＜0.05).After transfecting FKN-siRNA,the cellular invasive ability in the PANC-1 and SW-1990 FKN-siRNA group was significantly stronger than that in the control group and FKN-siRNA negative group(P＜0.05).After transfecting FKN-siRNA in cell lines PANC-1 and SW-1990,compared with the control group and FKN-siRNA negative group,the FKN protein and mRNA expression in the FKN-siRNA group was significantly decreased(P＜0.05),while IL-6 and STAT3 protein and mRNA expression was significantly increased(P＜0.05).Conclusion Chemokine FKN might play the inhibiting effect on the biological activity of pancreatic cancer cells by regulating IL-6/ STAT3 signal pathway.

Effects of chemokine Fractalkine on proliferation and invasion of human pancreatic cancer cell lines by regulating IL-6/STAT3 signal pathway / 重庆医学

Objective To explore the effects of chemokine Fractalkine(FKN) on the proliferation and invasion of human pancreatic cancer cell lines PANC-1 and SW-1990 by regulating IL-6/STAT3 signal pathway.Methods Adenovirus served as the vector to construct and synthesizing FKN-small interfering RNA(siRNA),then which was transfected into PANC-1 and SW-1990.The proliferation and invasion ability of cells was determined by CCK-8 assay and Transwell assay.Expression of FKN,IL-6 and STAT3 protein and mRNA was detected by Western blot and RT-qPCR.Results After transfecting FKN-siRNA for 24 h,the absorbance values(A value) in the PANC-1 and SW-1990 groups had no significant changes,the A value at 48,72 h in the FKN-siRNA group was significantly higher than that in the control group and FKN-siRNA negative group (P＜0.05).After transfecting FKN-siRNA,the cellular invasive ability in the PANC-1 and SW-1990 FKN-siRNA group was significantly stronger than that in the control group and FKN-siRNA negative group(P＜0.05).After transfecting FKN-siRNA in cell lines PANC-1 and SW-1990,compared with the control group and FKN-siRNA negative group,the FKN protein and mRNA expression in the FKN-siRNA group was significantly decreased(P＜0.05),while IL-6 and STAT3 protein and mRNA expression was significantly increased(P＜0.05).Conclusion Chemokine FKN might play the inhibiting effect on the biological activity of pancreatic cancer cells by regulating IL-6/ STAT3 signal pathway.

Characteristic of peripheral blood monocyte subsets and chemokines in early stage of acute coronary syndrome / 复旦学报（医学版）

Objective To investigate the expression of monocyte subsets and their chemokine,i.e.,monocyte chemoattractant protein (MCP-1) and fractalkine (FKN),in patients with acute coronary svndrome (ACS),and to analyze their correlation.Methods Patients with the syndrome of pectoralgia and to be inspected with coronary angiography (CAG) in our hospital from Sep.to Dec.,2016 were included.Patients' venous blood was collected on the operation day before operation,the level and proportion of monocyte (Mon) subsets,which was namely CD14 + CD16-Mon (Mon1),CD14+CD16 + Mon (Mon2) and CD14-CD16 + Mon (Mon3) according to the expression of cluster differentiation-14 (CD14) and CD16,were detected by flow cytometry (FCM).Patients' venous blood was collected on the operation day before operation and one day after operation,the concentrations of MCP-1 and FKN in plasma were measured by ELISA.We compared the expression levels of MCP-1-Mon1 and FKN-Mon3,and analyzed their relationship between each other respectively in different groups.Results Diagnosed according to the clinical symptoms,myocardial markers,electrocardiogram and CAG results,70 individuals were analyzed,including 30 patients with acute myocardial infarction (AMI group),25 patients with unstable angina pectoris (UAP group) and 15 patients with the chest pain symptoms and normal CAG results (control group).The percentage of Mon1 in the AMI group was higher than that in the other groups (P＜0.05);no difference was observed for Mon3 among the groups (P＞0.05).The Mon3/Mon1 ratio in the AMI group was lower than that in the control group (P＜0.05).Moreover,the levels of FKN and MCP-1 in the ACS group were greater than those in the control group.The level of red blood cell distribution width (RDW) was significantly increased in the AMI and UAP group than that in the control group (P＜0.05).There was a significant correlation between FKN and Mon3 (P＜0.05,R=0.650 2).Conclusions The monocyte subset of Mon1 and Mon3 increased in the early stage of ACS,with their chemokine (FKN and MCP-1) increasing at the same time.There is a significant correlation between FKN and Mon3,which indicates MCP-1-Mon1 and FKN-Mon3 may participate in the pathophysiological process of early ACS in patients.

Maturation Phenotype of Peripheral Blood Monocyte/Macrophage After Stimulation with Lipopolysaccharides in Irritable Bowel Syndrome

BACKGROUND/AIMS: Abnormal immune regulation and increased intestinal permeability augmenting the passage of bacterial molecules that can activate immune cells, such as monocytes/macrophages, have been reported in irritable bowel syndrome (IBS). The aim was to compare the maturation phenotype of monocytes/macrophages (CD14+) from IBS patients and controls in the presence or absence of Escherichia coli lipopolysaccharides (LPS), in vitro. METHODS: Mononuclear cells were isolated from peripheral blood of 20 Rome II-IBS patients and 19 controls and cultured with or without LPS for 72 hours. The maturation phenotype was examined by flow cytometry as follows: M1-Early (CD11c⁺CD206⁻), M2-Advanced (CD11⁻CD206⁺CX3CR1⁺); expression of membrane markers was reported as mean fluorescence intensity (MFI). The Mann-Whitney test was used and significance was set at P < 0.05. RESULTS: In CD14+ cells, CD11c expression decreased with vs without LPS both in IBS (MFI: 8766.0 ± 730.2 vs 12 920.0 ± 949.2, P < 0.001) and controls (8233.0 ± 613.9 vs 13 750.0 ± 743.3, P < 0.001). M1-Early cells without LPS, showed lower CD11c expression in IBS than controls (MFI: 11 540.0 ± 537.5 vs 13 860.0 ± 893.7, P = 0.040), while both groups showed less CD11c in response to LPS (P < 0.01). Furthermore, the percentage of “Intermediate” (CD11c⁺CD206⁺CX3CR1⁺) cells without LPS, was higher in IBS than controls (IBS = 9.5 ± 1.5% vs C = 4.9 ± 1.4%, P < 0.001). Finally, fractalkine receptor (CX3CR1) expression on M2-Advanced cells was increased when treated with LPS in controls but not in IBS (P < 0.001). CONCLUSIONS: The initial phase of monocyte/macrophage maturation appears to be more advanced in IBS compared to controls. However, the decreased CX3CR1 in patients with IBS, compared to controls, when stimulated with LPS suggests a state of immune activation in IBS.

Expression of fractalkine in acute lung injury induced by paraquat in rats / 中华急诊医学杂志

Objective To observe the expression of fractalkine (FKN or CX3CL1) in serum and lung tissue in early phases after paraquat (PQ) poisoning in rats,and to analyze the effect of FKN on acute lung injury induced by PQ.Methods A total of 66 SD rats were randomly (random number) divided into two groups,namely PQ group (n =36) and control group (n =30).Through intra-peritoneal route,PQ (22 mg/kg) was administered to PQ group,and an equal volume of normal saline to control group instead.Rats were separately sacrificed at 6 h,12 h,24 h,72 h and 120 h after poisoning.Lung coefficient was determined.The levels of FKN in serum and lung tissue homogenate were detected by ELISA.Lung pathological changes were observed by HE staining.FKN changes were investigated by immunohistochemistry staining.Data was analyzed by SPSS 19.0.Results From 6 h to 120 h after poisoning,parameter determined in PQ group had great changes,compared with the control group.At 6 h,12 h,24 h,72 h and 120 h,lung coefficients in PQ group were 5.03 ±0.07,5.17 ±0.10,5.46 ±0.10,5.68 ±0.15 and 5.83 ±0.11,respectively,which were significantly higher than those (4.49 ± 0.20,4.28 ± 0.13,4.45 ± 0.17,4.31 ±0.19 and 4.31 ±0.16) in control group (P＜0.01).Levels of FKN (pg/mL) in serum were 140.9 ± 15.8,157.9 ± 17.6,188.8 ± 24.8,224.4 ± 18.1 and 229.9 ± 10.0,respectively,significantly higher than those (121.7 ± 12.8,121.6 ± 12.1,118.3 ± 14.0,122.8 ± 12.4 and 120.5 ± 8.8) in control group (6 h P ＜0.05,others P ＜0.01).Levels of FKN (pg/mL) in lung tissue homogenate were 4 222.0 ± 641.1,5 021.0 ± 514.5,5 911.6 ± 478.1,7 092.2 ± 652.9 and 7 639.3 ± 666.6,respectively,significantly higher than those (2 860.2 ± 477.3,3 068.9 ± 446.0,3 168.7 ± 728.5,3 178.0 ±488.2 and 3 147.3 ±426.6) in control group (P ＜0.01).In PQ group,pathological changes manifested themselves in inflammatory cell infiltration,congestion,edema,structural damage,etc.The lung injury aggravated gradually from 6 h to 120 h.In control group,there was no significant change.FKN expressed mainly in bronchial cells,alveolar epithelial cells and pulmonary artery endothelial cells.Where there was higher expression of FKN,there were more inflammatory cells infiltrated.The level of FKN in lung tissue homogenate was positively correlated with lung coefficient (r =0.937).The level of FKN in serum was positively related to that in lung tissue homogenate (r =0.968).Conclusion There is correlation between FKN and acute lung injury induced by PQ in rats.

Effect of Chemotatic Factor FKN,PI3K and NF-κB on IL-6 Expression in Peripheral Blood Monocytes and the Effect of Valsartan Intervention / 中国医科大学学报

Objective To explore effect of irregular chemotatic factor fractalkine(FKN),phosphatidyl inositol 3 kinase and nuclear factor?κB(NF?κB)on interleukin?6(IL?6)expression in peripheral blood monocytes and the effect of valsartan intervention,so as to research the signal conduc?tive mechanism of FKN impacting on IL?6. Methods Peripheral blood monocytes were isolated from fresh blood of healthy volunteers by the densi?ty gradient centrifugation. The extractive peripheral blood monocytes were divided into seven groups:the control group,the FKN group,the LY294002 group(PI3K inhibitors),the PDTC group(NF?κB inhibitors),the FKN+valsartan group,the FKN+LY294002 group,and the FKN+PDTC group,the latter two were pretreated by LY294002 and PDTC respectively before FKN inducing PBMC cells. The IL?6 expression in cell me?dium was measured in each group by ELISA at 12 hours and 24 hours after PBMC treatment. Results After 12 hours of culture,compared with the control group,the expression of IL?6 in the FKN group was decreased(P0.05). Compared with the FKN group,the expression of IL?6 was decreased in the FKN+valsartan group(P0.05). Conclusion FKN can adjust the expression of peripheral blood PBMC IL?6 in a two?way pattern, inhibiting the expression of IL?6 by PI3K pathway and promoting the expression of IL?6 by NF?κB pathway,overall,FKN can inhibit the expression of IL?6. Valsartan can increase FKN to inhibit the expression of IL?6.

Research progression of Fractalkine/cx3cr1 and microglia in retina diseases / 中华实验眼科杂志

Fractalkine (Fkn) is the only member of CX3C subfamily of chemokine currently found,cx3cr1 is its specific receptor.Fkn/cx3cr1 is involved in inflammation,cancer,autoimmune diseases,allergy,acquired immune deficiency syndrome and other diseases,while its variety of pathophysiological role is accomplished by microglia.Functions of Fkn/cx3cr1 and microglia in age-related macular degeneration,acute light damage disease,retinal vascular disease,diabetic retinopathy disease,uveitis and other retina disease were reviewed in this article.

Investigation of Circulating Fractalkine and its Receptor CX3CR1 Levels in Patients With Chronic Congestive Heart Failure / 中国循环杂志

Objective: To observe the changes of circulating fractalkine and its receptor CX3CR1 level in patients with chronic congestive heart failure (CHF). Methods: Our work included 2 group, CHF group, n=55 patients and Control group, n=25 healthy subjects. Plasma level of soluble fractalkine (sFKN) was measured by ELISA, CX3CR1 in peripheral blood mononuclear cell was examined by lfow cytometry method. The relationship between sFKN and NT-proBNP was studied. Results: Compared with Control group, CHF group had increased sFKN level, P=0.004, and the patients with NYHY III, IV were more than NYHY II, and CHF group also had the higher CX3CR1 expression (14.7 ± 8.1), P Conclusion: The circulating FKN l and its receptor CX3CR1 might be involved in pathogenesis of immune-inlfammatory pathogenesis in CHF patients.

Effect of chronic intermittent hypoxia on the expression of fractalkine in rat liver / 中南大学学报(医学版)

Objective: To investigate the effect of chronic intermittent hypoxia (CIH) on liver injury and the expression of fractalkine in rats and explore its possible mechanism. Methods: A CIH murine model was established to mimic the pathophysiology of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. Thirty healthy male Spraque-Dawley rats were randomly assigned to 3 groups: a 5% CIH group, a 5% CIH+RH (removal of hypoxia) group and a control group ( 10 rats in each group). The 5% CIH and 5% CIH+RH groups were exposed to CIH for 3 weeks, 8 h/d, and the frequency of hypoxia was 20 times/h. The 5% CIH+RH group was then exposed to normal gaseous environment for another 3 weeks. After the experiment, liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of fractalkine in the liver tissues was detected by immunohistochemical method. Results: 1) Compared with the control group, the hepatic steatosis and inflammatory activities in the 5% CIH and 5% CIH+RH groups were more severe (allP Conclusion: CIH can induce liver injury and high fractalkine expression in rat liver tissues.

Investigation of the Expression of Fractalkine and the Infiltration Characteristics of Fractalkine Receptor Positive Cells and Macrophages in Cisplatin-induced Acute Renal Failure in Mice / 대한신장학회지

PURPOSE: The aim of the present study was to investigate the expression and the infiltration characteristics of fractalkine (CX3CL1)/ its receptor (CX3CR1) positive cells and macrophages in cisplatininduced ARF (CisARF). METHODS: Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice. Time course of CX3CL1 expression/CX3CR1 positive cells and macrophage infiltration in CisARF was investigated by using immunofluorescence for CX3CL1, CX3CR1 and CD 11b in the outer medullary region. And we performed a study whether there was a significant difference of macrophages infiltration between wild type and caspase-1- deficient mice, which was protective against CisARF. RESULTS: (1) Renal dysfunction was the most severe on day 3. (2) The intensity of immunofluorecence staining for CX3CL1 showed that there was a significantly increased expression in the tubulointerstitium rather than blood vessels in cisplatin-treated mice. There were no differences in CX3CR1 positive cells between vehicle and cisplatin-treated mice. (3) Macrophages infiltration was augmented from day 2 after cisplatin administration and preceded the development of CisARF. Macrophages infiltration in caspase-1 -/- mice was significantly lower than wild- type mice in CisARF. CONCLUSION: Our data demonstrated that CX3CL1 expression and macrophage infiltration in CisARF precedes the development of ARF, especially in the tubulointerstitium rather than blood vessels. However, recent reports showed that the blockade of CX3CR1 positive cells and depletion of macrophages could not be protective against CisARF. Therefore, further study is required to determine the role of other inflammatory cells such as natural killer cells in CisARF.

On the expression of fractalkine by rosiglitazone in human renal mesangial cells induced by advanced glycation end products / 中华内分泌代谢杂志

The effect of rosiglitazone and advanced glycation end products (AGEs) on the expression of fractalkine in cultured human renal mesangial cells (HRMC) were investigated. Rosiglitazone inhibits the upregulation of fractalkine induced by AGEs in HRMC.

Chemokine Fractalkine Induced Monocytes Adhesion on Human Umbilical Vascular Endothelial Cells / 中华高血压杂志

Background Fractalkine(FKN) is a novel chemokine that mediate the adhesion of monocyte to vascular endothelial cell,involving in the development of atherosclerosis(AS).Objective To investigate the effect of interleukin-18(IL-18) on the fractalkine expression in human umbilical vascular endothelial cells(HUVEC),and the role of fractalkine in the monocytes THP-1 adhesion on HUVEC.Methods Fractalkine expression in HUVEC was determined by reverse transcription-polymerase chain reaction(RT-PCR),and the adhesion of THP-1 to HUVEC was assessed by Flow Chamber.Results Incubation of HUVEC with IL-18 upregulated FKN mRNA expression in dose-dependent manner.In the concentration of IL-18 ranged 0,25,50,100 ?g/L,the FKN mRNA was increased from(0.10?0.01),(0.49?0.04),(0.63?0.09) to(0.85?0.07)(P trend

Aspirin Inhibits Fractalkine Expression Stimulated by Tumor Necrosis Factor ? in Human Umbilical Vein Endothelial Cells / 中华高血压杂志

Background Fractalkine is involved in the impairment of endothelium by mediating inflammatory cell chemotaxis.Aspirin inhibites many kinds of cytokine expression.Objective To investigate the effect of aspirin on tumor necrosis factor ?(TNF-?) stimulated fractalkine expression in human umbilical vein endothelial cells (HUVEC) and its mechanism.Methods HUVEC were grouped as follows:control group;TNF-?-stimu- lated;TNF-?+NS-398;TNF-?+PDTC and TNF plus various concentration of aspirin (0.02,0.2,1.5 mmol/L). The level of mRNA and protein expression of fractalkine and nuclear factor(NF)-kB p65 was determined by RT- PCR and Western blot.Results 1)Fractalkine mRNA and protein level was increased after 4 ?g/L TNF-? stim- ulation in HUVEC(both P

Simvastatin inhabits the adhesion and expression of chemokine fractalkine in human umbilical vascular endothelial cells induced by interleukine-18 / 中国药理学通报

Aim To investigate the effect of simvastatin on the FKN expression in human umbilical vascular endothelial cells(HUVEC)up-regulated by interleukine-18(IL-18),and the effect on adhesion of FKN to monocyte THP-1.Methods FKN expression in HUVEC was determined by reverse transcription-polymerase chain reaction (RT-PCR), and the adhesion was checked by in vitro Flow chamber.Results Incubation of HUVECs with IL-18 upregulated FKN mRNA expression(P

Effect of fractalkine on neuroprotection / 中国病理生理杂志

The chemokine fractalkine primarily involves in chemotaxis,adherence and inflammation.Recently it has been discovered owning the ability of inhibiting cell death in neurons and glial cells,as well as protecting central nervous system from toxic damage.Fractalkine reduces the toxicity to neurons and glial cells mediated by excessive Fas L,glutamate(Glu) or lipopolysaccharide(LPS).In vivo neutralization of endogenous brain fractalkine signal pathway increases inflammatory cytokines secretion and neuronal cell death induced by LPS.Fractalkine may achieve its neuroprotective property through influencing expression of pro-apoptotic and anti-apoptotic proteins,intracellular Ca2+ level and inflammatory cytokines secretion via protein kinase B(PKB)/Akt and extracellular signal-regulated kinase(ERK)/MAPK pathways.