Role of chemokine CXC-ligand 16 in renal fibrosis following renal ischemia-reperfusion injury in mice / 中华麻醉学杂志

Objective To evaluate the role of chemokine CXC-ligand 16 (CXCL16) in renal fibrosis following renal ischemia-reperfusion (I/R) injury in mice.Methods Twenty-four healthy male C57BL/6 mice,aged 8-10 weeks,weighing 20-30 g,were divided into 4 groups (n =6 each) using a random number table method:sham operation group (group S),sham operation plus anti-CXCL16 antibody group (group S+A),group I/R,and I/R plus anti-CXCL16 antibody group (group I/R+A).Renal ischemia was induced by occlusion of the left renal artery for 30 min followed by 72-h reperfusion,and the fight kidney was removed on 5th day in anesthetized mice.CXCL16 antibody 5 mg/kg and the equal volume of normal saline were intraperitoneally injected at 72 h after reperfusion twice a week for 2 consecutive weeks in I/R+A and I/R groups,respectively.Sham operation was performed,and the equal volume of CXCL16 antibody 5 mg/kg and normal saline were intraperitoneally injected at 72 h after reperfusion twice a week for 2 consecutive weeks in S+A and S groups,respectively.Orbital venous blood samples were collected at day 14 after reperfusion for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.Animals were then sacrificed and the left kidney was removed for measurement of the renal fibrosis size (using Sirius red staining),expression of t-smooth muscle actin (α-SMA),fibronectin (FN) and type Ⅰ collagen (Col-Ⅰ) in renal tissues by Western blot.Results Compared with group S,the serum BUN and Cr concentrations and renal fibrosis size were significantly increased,and the expression of α-SMA,FN and Col-Ⅰ was up-regulated in group I/R (P＜0.05).Compared with group I/R,the serum BUN and Cr concentrations and renal fibrosis size were significantly decreased,and the expression of α-SMA,FN and Col-Ⅰ was down-regulated in group I/R+A (P＜0.05).Conclusion CXCL16 is involved in the process of renal fibrosis following renal I/R injury in mice.

Research advances on relationship between CXC chemokine ligand 10 and viral hepatitis / 中华临床感染病杂志

In the progress of viral hepatitis, lymphocytes migrate and infiltrate liver tissues, which is relevant to antiviral therapy.However, the related mechanism is still poorly understood.In recent years,CXC chemokine ligand (CXCL)10 and its receptor CXCR3 have been extensively studied.The interaction between CXCL10 and CXCR3 would be a breakthrough point for study of the mechanism of viral hepatitis pathogenesis.This article reviews the research advances of CXCL10 in the progression of viral hepatitis and in the evaluation of antiviral therapy.

Role of chemokine CXC-ligand 16 in renal ischemia-reperfusion injury in mice / 中华麻醉学杂志

Objective To investigate the role of chemokine CXC-ligand 16 (CXCL16) in renal ischemia-reperfusion (I/R) injury in the mice.Methods Twelve healthy male C57BL/6 mice and 12 CXCL16-knockout (CXCL16-KO) mice,aged 8-10 weeks,weighing 20-30 g,were studied.The 12 C57BL/6 mice were randomly divided into 2 groups (n=6 each) using a random number table:C57BL/6 sham operation group (group C-S) and C57BL/6 I/R group (group C-I/R).The 12 CXCL16-KO mice were randomly divided into 2 groups (n=6 each) using a random number table:CXCL16-KO sham operation group (group KO-S) and CXCL16-KO I/R group (group KO-I/R).The right kidney was removed,and the left kidney was exposed,and the renal artery was then clamped for 45 min with atraumatic microclips followed by 24 h reperfusion to establish the model of renal I/R in anesthetized mice.Venous blood samples were taken at 24 h of reperfusion for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The renal specimens were obtained at 24 h of reperfusion for microscopic examination of the pathological changes,and the damage to the renal tubules was scored.The number of myeloperoxidase (MPO) positive cells (MPO+ cells),F4/80+ cells and CD3+ cells in renal tissues was counted by immunohistochemistry.The expression of tumor necrosis factor-alpha (TNF-α),interleukin-1beta (IL-1β),IL-6,and macrophage inflammatory protein-2 (MIP-2) mRNA in renal tissues was determined by real-time reverse transcriptase polymerase chain reaction.Results Compared with group C-S,the serum BUN and Cr concentrations,renal tubular damage score,and the number of MPO+,F4/80+,and CD3+ cells were significantly increased,and the expression of TNF-α,IL-1β,IL-6 and MIP-2 mRNA was significantly up-regulated in group C-I/R (P＜0.05).Compared with group KO-S,the serum BUN and Cr concentrations,renal tubular damage score,and the number of MPO+,F4/80+,and CD3+ cells were significantly increased,and the expression of TNF-α,IL-1β,IL-6 and MIP-2 mRNA was significantly up-regulated in group KO-I/R (P＜0.05).Compared with group C-I/R,the serum BUN and Cr concentrations,renal tubular damage score,and the number of MPO+,F4/80+,and CD3+ cells were significantly decreased,and the expression of TNF-c,IL-1β,IL-6 and MIP-2 mRNA was significantly down-regulated in group KO-I/R (P＜0.05).Conclusion CXCL16 is involved in the pathophysiological process of renal I/R injury in the mice.

Roles of PI3K signaling pathway in IL-8/CXCR2-mediated growth and metastasis of liver cancer / 中国医师杂志

Objective To explore the role of phosphatidylinositol 3-kinase (PI3K) signal pathway in interleukin-8 (IL-8)/chemokine (C-X-C Motif) receptor 2 (CXCR2)-mediated growth and metastasis of liver cancer.Methods Eighty-two cases of liver cancer tissues and serum samples,and 21 cases of normal tissues and serum samples were collected.The level of serum IL-8 was measured by enzyme-linked immunesorbent assay (ELISA).Expression of CXCR2 was detected by immunohistochemical method,and its correlation with clinicopathological parameters was also analyzed.Different stages of liver cancer fresh tissues were selected,and expressions of CXCR2,PI3Kγ,AKT,and NF-κB were detected by Westeru blotting analyses.Results The levels of serum IL-8 in liver cancer patients (stages Ⅰ,Ⅱ,Ⅲ,Ⅳ) were (120.34 ±15.52) pg/ml,(221.60 ±23.10) pg/ml,(279.50 ±24.25) pg/ml,(324.81 ±22.50) pg/ml,respectively.With the increasing degree of liver cancers,levels of IL-8 were increased,most significant was in the Ⅳ period of liver cancer; the expression of CXCR2 was significantly correlated with pathological stages,degree of differentiation,lymph node and distant metastases of liver cancer (P ＜ 0.05) ; serum IL-8 levels were consistent with expression of CXCR2 in liver cancer tissues,which had a strong correlation with activation of PI3K γ,AKT,and NF-κ B proteins.Conclusions IL-8/CXCR2 was able to mediate the growth and metastasis of liver cancers,which might be through the activation of PI3K signaling pathway.

Expression and role of chemokine CXCL11 in pancreas of rats with acute necrotizing pancreatitis / 中华胰腺病杂志

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.

Expressions and significances of CXCR4 and CD133mRNA in primary lesion of gastric adenocarcinoma / 国际外科学杂志

ObjectiveTo investigate the expression of CXCR4 and CD133mRNA in primary lesion of primary gastric adenocarcinoma and the relation with clinicopathological features,and to explore the correlation of CXCR4 and CD133.MethodsThe primary lesion of primary gastric adenocarcinoma and normal tissues adjacent to gastric cancer were obtained from 50 patients.The diction of CXCR4 and CD133 protein expression was detected by the immunohistochemical staining,and the relative gray scale values of CXCR4 and CD133mRNA by semi-quantitative RT-PCR (Fisher' s exact probability method).Their relationship with clinicopathological features was also investigated ( Spearman relation analysis).ResultsThe positive rates of CXCR4 and CD133 protein in gastric cancers were 76.0％ and 66.0％ respectively,which were significantly higher than that in normal tissues adjacent to gastric cancer ( 16.0％ and 10％ ; P =0.000,P =0.000).The increment of relative gray scale values of CXCR4mRNA was associated with the larger tumor diameter,the later TNM stage and the occurrence of lymphatic metastasis( P ＜ 0.05 ).And the larger diameter of tumor,the later TNM stage were associated with the higher relative gray scale values of CD133mRNA (P ＜0.05).The levels of the relative gray scale values of CXCR4 mRNA and CD133mRNA were positively related(r =0.453,P ＜ 0.01 ).ConclusionsThe higher expression of CXCR4 and CD133mRNA correlateswith tumour diameter,TNM stage and lymphatic vessel invasion. The relative gray scale values of CD133mRNA increase with the increment of the relative gray scale values of CXCR4.

Relationship between serum CXCL16 levels and stroke subtypes in patients with acute cerebral infarction / 国际脑血管病杂志

Objective To investigate the changes of serum CXCL16 levels in patients with acute cerebral infarction and their relationship with the Trial of Org10172 in Acute Stroke Treatment (TOAST) etiological types of cerebral infarction. Methods The serum CXCL16 levels in 113 patients with acute cerebral infarction were measured by enzyme-linked immunosorbent assay (ELISA), and they were grouped according to TOAST types. The patients between all the subgroups and/or 32 healthy controls were compared. Results The serum CXCL16 levels in patient group were significantly higher than those in control group (2.29 ± 0.21 ng/mlvs.1.75±0.21 ng/ml, t= 12.863, P= 0.000); The serum CXCL16 levels in large artery atherosclerotic (LAA) stroke group were significantly higher than those in small artery occlusive (SAO) stroke group (2.38 ±0.23 ng/mL vs. 2.21 ±0.11 ng/ml, 1 =5. 743, P =0. 000), and both were significantly higher than those in the control group (q = 20. 501, P = 0. 000; q =13. 527, P= 0. 000). In the LAA group, there were no significant differences between the serum CXCL16 levels in ≥2 artery stenosis group and those in only 1 artery stenosis group (2.34 ±0.24 ng/ml vs. 2.46 ± 0. 19 ng/ml, t = - 1.969, P = 0. 054). Multivariate logistic regression analysis showed that CXCL16 (OR =0.972, 95% CI0.956-0. 978, P =0.001)and hyperlipidemia (OR =3.547, 95%CI 1.160-10. 848, P=0. 020) were the independent risk factors for cerebral infarction. Conclusions The serum CXCL16 levels increased in acute cerebral infarction, it closely related with the occurrence of cerebral infarction, and the LAA stroke group was significantly higher than the SAO stroke group.

Influences of ultraviolet A (UVA) on the secretion and expression of chemokine CXCL11/I-TAC by HaCaT cells / 中华皮肤科杂志

Objective To investigate the influences of UVA on the secretion and expression of chemokine CXCL11/I-TAC by HaCaT cells induced by interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α). Methods HaCaT cells were cultured in the presence of IFN-7 and TNF-a and irradiated with UVA of 2, 4 and 8 J/cm~2, respectively; those cells receiving neither treatment with IFN-γ or TNF-α nor UVA irradiation served as the negative control, and those receiving only cytokine treatment but no irradiation as the positive control. After another 24-hour culture, enzyme-linked immunosorbent assay (ELISA) was performed to detect the protein levels of CXCL11/I-TAC in the supernatant of HaCaT celb, real time PCR to measure the mRNA expression of CXCL11/I-TAC in these HaCaT cells. Results As far as the negative control HaCaT cells were concerned, there was a minor secretion of CXCL11/I-TAC protein and expression of CXCL11/I-TAC mRNA. After treatment with IFN-7 and TNF-a of 10 μg/L, the protein and mRNA expressions of CXCL11/ I-TAC were synergistically upregulated, whereas the induced secretion and expression of CXCL11/I-TAC by HaCaT cells were dose-dependently inhibited by UVA irradiation. Conclusions UVA irradiation inhibits the secretion and expression of CXCL11/I-TAC by HaCaT cells, which in turn suppresses the chemotaxis of Th1/ Tel cells in some degree.

Effects of the CXCR3-inhibitor Genistein on the acute rejection of pancreas transplantation in a rat model / 中华胰腺病杂志

Objective To investigate the effects and mechanisms of the CXCR3-inhibitor genistein on the acute rejection reaction of pancreas transplantation in a rat model. Methods Three groups of rats underwent pancreas transplantation, group one: the syngeneic transplantation group; group two: heterogous transplantation group without genistein-treatment; and group three: genistein-treatment (10 mg/kg,i. p.×7d) transplantation group. The grafts of three groups were harvested at day 7 after operation for histopathology and immunohistochemistry analysis of CXCR3, the serum levels of IFN-γ, IL-2 were examined by ELISA. Results There was no acute rejection reaction of pancreas transplantation in group one and no expression of CXCR3 ,the serum levels of IFN-γ,IL-2 were (2.76±0.66) pg/ml and (11.83±1.86) pg/ml. In group two, there was significant acute rejection reaction and strong expression of CXCR3, the serum levels of IFN-γ, IL-2 were (32.64±2.52) pg/ml and (29.59±1.71 ) pg/ml, which were significantly higher than those in group one (P<0.05). Compared with group two, the damages of graft tissue in genistein-treatment group alleviated and the lymphocytes infiltration decreased, the expression of CXCR3 was weakly positive, the serum levels of IFN-γ, IL-2 were (15.94±1.95) pg/ml and (22.62±1.76) pg/ml, which were significantly lower than those in group two(P<0.05), but was higher than those in group one (P<0.05). Conclusions Genistein could mitigate the acute rejection of pancreas transplantation effectively through inhibiting CXCR3 expression.

Expression and significance of chemokine CXC receptor 3, 4 and their ligands at the early pregnancy decidua and villi / 中华妇产科杂志

Objective To explore the expression and significance of chemokine CXC reeeptor (CXCR)3 and CXCR4 and their ligands(CXCL)at the early pregnancy decidua and villi.Methods Decidual mononuclear cells were isolated from the normal decidua of 5-8 weeks pregnant women by lymphocyte separation medium in vitro.CD56+natural killer(NK)cells were purified by dynabeads cell sorter kiL Purity and phenotype of CD56+decidua NK cells were analyzed by fluorescence-activated eell sorter (FACS).Gene expression of CXCR3 and CXCR4 in decidua NK cells and CXCL9,CXCL10 and CXCL12 in early pregnancy decidua and villi was assessed bv RT.PCIZ Protein expression of CXCL9,CXCL10 in normal endometrium and early pregnancy decidua was characterized and quantified by streptavidin-biotin pemxidase chain reaction(SP)immunohistochemistry and computered image analysis system.Correlations between the gray degree of CXCL9 and CXCL10 and the number of CD56+NK cells in upper tissue were analyzed by Spearman's correlation ceefficient rank tesL Results The phenotype of 98.7%decidua NK cells was CD56bright.The genes of CXCR3 and CXCR4 were expressed in decidua NK cells and that of CXCL9 and CXCL1O were expressed in early pregnancy decidua and CXCLI2 in early pregnancy villi.CXCL9 and CXCL10 were expressed in the cytoplasm of surface epithelia,glandular epithelia and stromal cells of early pregnancy deeidua and were not expressed in villi by immunohistochemistry.The gray degree of CXCL9 and CXCL10 in the secretory phase endometrium(56±43,59±47)was stronger than that in the proliferative phase(16±18,8±14,P<0.05)and reached the highest(143±35,158±29,P<0.05)in the early pregnancy decidua.The number of cD+56 NK cell in the secretory phase endometrium(60±20)was more than that in the proliferative phase endometrium(23±4,P<0.05)and was the most in the early pregnancy decidua(114±15,P<0.05).The gray degree of CXCL9 in upper tissue had a positive correlation with the number of CD+56 cells(r=0.88,P<0.05)and that of CXCL10 had a similar pattern to CXCL9(r=0.86,P<0.05).Condusion The interactions between CXCL9,CXCL10 and CXCL12 expressed in decidua and villi and CXCR3,CXCR4 expressed in CD+56 decidua NK cells may influence the CD+56 NK cell recruitment at the maternal-fetal interface.

Correlation of HPA and CXCR4 expressions with the invasion and metastasis of hepatocellular carcinoma / 肿瘤

Objective: To investigate the expressions of heparanase (HPA) and chemokine receptor 4 (CXCR4) in hepatocellular carcinoma (HCC) and their correlations with the invasion and metastasis of HCC. Methods: The expressions of HPA and CXCR4 in HCCs, peri-cancerous tissues, and normal liver tissues were detected by immunohistochemical method. Statistical analysis was used to determine the relationship between their expressions and clinicopathological features. Results: HPA and CXCR4 were over-expressed in HCC tissues compared with that in peri-cancerous tissues and normal liver tissues (P<0.05). The expressions of HPA in HCC correlated with tumor size, intrahepatic or lymphatic metastasis and tumor differentiation (P<0.05); the expression of CXCR4 in HCC correlated with intrahepatic or lymphatic metastasis and tumor thrombosis (P<0.05). There was a positive relationship between HPA and CXCR4 expression (r = 0.313, P=0.027). Conclusion: HPA and CXCR4 play a synergistic role in the initiation, progression, invasion, and metastasis of HCC.

Expressions of stromal cell-derived factor-1 and CXCR4 in endometrial carcinoma tissues and cell lines / 北京大学学报(医学版)

Objective: To investigate the expressions of SDF-1 and CXCR4 in human endometrial carcinoma tissues. Methods: SDF-1 and CXCR4 protein expression levels were detected by immunohistochemical staining in 26 cases of atypic hyperplasia endometrium,simple hyperplasia endometrium and normal endometrium and 44 cases of endometrial carcinoma tissues. Results: Both SDF-1 mRNA and CXCR4 mRNA were expressed in Ishikawa, while no expression of SDF-1 mRNA was detected in HEC-1A.The rates of CXCR4 and SDF-1 protein expressions were 100% in glandular cells of human normal endometrial tissues, while 90.9% and 93.2% in glandular cells of endometrial carcinoma tissues.These immunoreactivities of SDF-1 and CXCR4 were significantly low in endometrial carcinoma tissues as compared with those in normal endometrium;and the intensities of immunohistochemical staining significantly decreasesd in immunoreactivity of SDF-1 and CXCR4 in low grade as compared with that in hight grade. Conclusion: SDF-1 and CXCR4 were expressed differently in endometrial cell lines, human normal endometrial tissues,and endometrial carcinoma tissues. As compared with normal endometrium ,these were significantly low levels expression of SDF-1 and CXCR4 in endometrial carcinoma tissues.

Production of Stromal Cell-Derived Factor-1 (SDF-1)and Expression of CXCR4 in Human Bone Marrow Endothelial Cells

This study investigated the production of stromal cell-derived factor-1 (SDF-1) and the expression of CXCR4 in human bone marrow endothelial cells (BMECs). Human BMEC cell line BMEC-1 cells expressed SDF-1 mRNA, and conditioned medium induced chemoattraction of CD34+ cells. Migration was not inhibited by pretreating the input cells with pertussis toxin, indicating that the chemoattractive activity was not dependent on SDF-1. Three-day culture of BMEC-1 and primary human BMEC cells produced 1,710+/-204 and 1,050+/-153 pg/mL SDF-1alpha, respectively, which was much less than primary human BM stromal cells (29,536+/-532 pg/ mL). By immuno-histochemistry, CXCR4 was detected in the endothelial cells lining sinusoids, arterioles, and venules in the bone marrow. However, cultured BMECs and BMEC-1 cells did not express CXCR4 on their surfaces. These results indicate that BMECs produce and release small amounts of SDF-1 and express CXCR4 in vivo only.

Modulatory effect of curcumin on the adhesion and migration of Raji cells / 中国医师杂志

Objective To study the effect of SDF1/CXCR4 and FN/?1 integrin modulated by curcumin on the adhesion and migration of B lymphoma Raji cell and to explore the mechanism of curcumin to inhibit the invasiveness of lymphoma.Methods The experiment consisted of eight groups: Control,FN,SDF,FN+anti-?1 integrin,SDF+anti-CXCR4,curcumin+FN,curcumin+SDF.Adhesion assay and migration assay were used to detect the difference of invasiveness among different groups.Results In vitro,SDF1 and FN can increase the adhesion and migration of Raji cells,which can be blocked by ?1 integrin antibody and CXCR4 antibody.Curcumin can inhibit the adhesion and migration of Raji to FN in a dose-dependant manner.Low dosage curcumin had minimal effect on the adhesion and migration of Raji induced by SDF except that 25?mol/L curcumin can inhibit the adhesion and migration of Raji.Conclusion FN/?1 integrin and SDF1/CXCR4 pathway play important roles in the adhesion and migration of Raji cells.Curcumin can decrease the invasiveness of Raji cells through inhibiting FN/?1 integrin.It has good prospect of clinical application.

Serum Level of Interferon-inducible T Cell Alpha Chemoattractant(I-TAC)in Patients With Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To determine the relationship between serum interferon-inducible T cell alpha chemoattractant(I-TAC)levels and disease activity in patients with systemic lupus erythematosus(SLE).Methods Serum level of I-TAC was measured by sandwich ELISA.Results①Serum level of I-TAC was significantly increased in patients with SLE as compared with controls,and significantly higher in patients with active SLE than those of the inactive.Serum level of I-TAC showed significant positive correlation with disease activity,erythrocyte sedimetation rate(ESR),logarithm of serum ANA titer,and negative correlation with serum C3levels.②Serum level of I-TAC was significantly higher in patients with renal involvement than those without renal diseases.Conclusions These results suggest that I-TAC might be involved in the pathogenesis of SLE,and its serum level might be used as a good indicator for the disease activity of SLE and renal involvement.