RESUMEN
@#[摘 要] 恶性肿瘤是严重威胁人类生命的疾病之一，近年来免疫治疗已经成为肿瘤治疗的焦点，解决免疫治疗只对部分患者有效的问题迫在眉睫。在肿瘤微环境（tumor microenvironment，TME）中趋化因子介导细胞的定向移动，同时具有多种调节功能，既可以作用于免疫细胞，也可直接作用于肿瘤细胞，发挥了复杂的生物学作用。CXC趋化因子受体3（CXC chemokine receptor 3，CXCR3）通过与其同源CXC趋化因子配体9（CXC chemokine ligand 9，CXCL9）/10/11结合，不仅参与了肿瘤发生、侵袭并促进肿瘤相关血管的形成，同时也介导了免疫细胞向肿瘤组织中浸润，为无免疫反应性或免疫反应性差的“冷肿瘤”转变为免疫反应性的“热肿瘤”提供了新的思路，并且可能成为治疗的新靶点。这种抗肿瘤和促肿瘤的双重作用，似乎与CXCR3变体（CXCR3-A、CXCR3-B）发挥相反的作用密切相关。本文就近年来CXCR3变体CXCR3-A、CXCR3-B及其配体CXCL9/10/11在TME中作用的研究进展展开综述。
RESUMEN
@#AIM: To investigate the effects of exogenous CXCL9, CXCL10 and CXCL11 on human umbilical vein endothelial cells under a high glucose environment and explore its mechanisms.<p>METHODS: The cells in logarithmic growth stage were divided into control group(glucose concentration 5.5mmol/L), low glucose group(glucose concentration 5mmol/L), high glucose group(glucose concentration 30mmol/L). CXCL9(100ng/mL), CXCL10(10ng/mL)and CXCL11(100ng/mL)were added respectively, cultured for 24, 48 and 72h. CCK-8 method was used to detect cell proliferation, RT-PCR was used to detect CXCR3 mRNA expression, and immunofluorescence was used to detect Ki-67 expression.<p>RESULTS: The results of CCK-8 method showed that the absorbance value of the control group increased gradually with the increase of time after adding three exogenous chemokines. The absorbance value of the low glucose group increased first and then decreased, reaching the peak at 48h. The absorbance value of the high glucose group decreased generally. The results of RT-PCR showed that the expression of CXCR3 mRNA in low glucose group and high glucose group was higher than that in 24h after adding CXCL9, CXCL10 and CXCL11 for 48 and 72h. The results of immunofluorescence showed that the fluorescence intensity of Ki-67 decreased in the low and high glucose 72h after adding CXCL9, CXCL10 and CXCL11. The change in the high glucose group is more obvious.<p>CONCLUSION: Exogenous CXCL9, CXCL10 and CXCL11 can decrease the activity of human umbilical vein cell under high glucose environments and induce the increase in CXCR3 expression. The increase of CXCR3 reached the highest after adding exogenous CXCL10 and CXCL11, suggesting a target for clinical intervention of diabetic retinopathy.
RESUMEN
Objective: To investigate the important role of NF-κB pathway in CXCL11-induced invasion and epithelial-mesenchymal transition (EMT) of pancreatic cancer cell line Panc-1. Methods: Panc-1 cultured in vitro was harvested and divided into control group, CXCL11 group, and BAY 11-7082 group (NF-κB inhibitor). Transwell invasion assay was applied to analyze the invasive ability of tumor cells in different groups. The expressions of p65, P-p65, E-cadherin, N-cadherin, and Vimentin were determined by Western blot. The intracellular localization of p65 was detected by immunofluorescence staining. Results: CXCL11 significantly induced the invasion of Panc-1 cells, promoted p65 nuclear translocation of Panc-1 cells, upregulated the expressions of P-p65, N-cadherin and Vimentin, and downregulated the expression of E-cadherin. Furthermore, the inhibition of NF-κB pathway obviously abrogated CXCL11-induced invasion of Panc-1 cells and enhanced the p65 nuclear translocation. Conclusion: CXCL11 induces epithelial-mesenchymal transition and enhances invasion of pancreatic cancer cells through the activation of NF-κB pathway.
RESUMEN
Objective To investigate the dynamic expressions of CXCL11 and its role in the pathogenesis of acute necrotizing pancreatitis (ANP).Methods Forty-eight SD rats were randomly divided into control group and ANP group,with 24 rats in each group.ANP model was induced by retrograde injection of 4％ sodium taurocholate (1 ml/kg body weight) into the biliary and pancreatic duct.The rats were sacrificed at 1,3,6,12 hours.Serum level of amylase was determined,pathological changes in pancreatic tissue were routinely observed and scored.The expression of CXCL11 mRNA and proteon in pancreas was measured by fluorescence quantitative polymerase chain reaction and immunohistochemical method.The serum levels of CXCL11 were measured by enzyme-linked immunoadsorbent assay.Results The serum levels of amylase in ANP rats were significantly higher than those in control group [(6153 ± 355)U/L vs (185 ± 32)U/L at 6 h,P ＜0.05],pathological changes in pancreatre tisues were more significant in ANP rats,and the pathological score was significantly higher than that in control group [(9.00 ± 0.63) vs (0.33 ± 0.12) points at 6 h,P ＜ 0.05] ; the expressions of CXCL11 mRNA and protein in pancreatic tissue were significantly increased than those in control group (3.13 ± 0.43 vs 0.99 ± 0.24,2.76 ± 0.27 vs 0.33 ± 0.12 at 6 h,P ＜ 0.05).The serum level of CXCL11 was significantly higher than that in control group [(112.1 ± 14.2)ng/L vs (56.8 ±4.3) ng/L at 6 h,P ＜0.05)].Conclusions CXCL11 is an early inflammatory mediator in acute pancreatitis,and involved in the pathogenesis of ANP in rats.
RESUMEN
Objective:To investigate the expression of Th1 chemokine CXCL9,CXCL10,CXCL11,Th2 chemokine CCL22 and their receptors in the lesions of bullous pemphigoid (BP).Methods:Immunohistochemical assay was performed to detect the expression of CXCL9,CXCL10,CXCL11,CCL22 and their receptors CXCR3 and CCR4 in BP lesions and normal control skin.Results:CXCL9,CXCL10,CXCL11,CCL22,CXCR3 and CCR4 were overexpressed in BP lesions than those in normal control skin (P＜0.01).The positive rates of CXCL9,CXCL10,CXCL11 and CXCR3 in BP lesions were 50%(15/30),46.7%(14/30),46.7%(14/30) and 53.3%(16/30),respectively.The positive rates of CCL22 and CCR4 were 66.7% (20/30) and 56.7% (17/30).Conclusion:The overexpression of Th1 chemokine CXCL9,CXCL10,CXCL11,Th2 chemokine CCL22 and their receptors may play important roles in the pathogenesis of BP.
RESUMEN
BACKGROUND: CXCL10 and CXCL11, which are family of CXCR3 ligands, are expressed by lymphocytes and even by bronchial epithelial cells if the cellular immunity is activated. This study evaluated the potential utility of CXCL10 and CXCL11 in the serum for active pulmonary tuberculosis in comparison with lung cancer, which activates the cellular immunity, and benign lung diseases. METHODS: Patients who newly visited Pusan National University Hospital from January 2007 to December 2007 and were suspected of having lung cancer or tuberculosis were enrolled prospectively. The patients were classified pathologically and clinically into three groups, 47 with lung cancer, 18 with active pulmonary tuberculosis and 38 control patients with benign pulmonary disease. ELISA was used to determine the levels of CXCL10 and CXCL11 were determined in the serum. RESULTS: The level of CXCL10 and CXCL11 were significantly higher in the active pulmonary tuberculosis group than in the lung cancer and benign lung disease groups (p<0.001, Kruskal-Wallis). The level of CXCL11 was significantly higher in the lung cancer group than in the benign pulmonary disease group, but there was no significant difference in level of CXCL10 between the three groups (p<0.001, p=0.655, respectively, Mann-Whitney U). The level of CXCL10 in patients with stage III+IV lung cancer was significantly higher than those with stage I+II, but there was no significant difference in the level of CXCL11 between the groups (p<0.001, p=0.07, respectively, Mann-Whitney U). There was no significant difference in the level of CXCL10 and CXCL11 between those with the presence and absence of lung cancer metastasis. There was a significant correlation between the level of CXCL10 and CXCL11 (r=0.223, p<0.001). CONCLUSION: CXCL10 and CXCL11 may be a potential useful markers for active pulmonary tuberculosis if used alongside other diagnostic methods.