Objective To understand role of chemokines and their receptors in pathogenesis, progression, and metastasis of gastric cancer, and to provide a better approach for diagnosis and treatment of gastric cancer. Method The literatures about the relationship between chemokines and their receptors and gastric cancer were reviewed. Results There were about 50 various chemokines and their receptors abnormally expressed in the tumor microenvironment. The main types related gastric cancer were the CXC, CC and CX3C chemokines and their receptors, which could promote the proliferation, invasion, and metastasis of the gastric cancer through several pathways like mTOR pathway, JAK2-STAT3 pathway, etc.. Conclusions Chemokines and their receptors play an important role in occurrence and development of gastric cancer. Further studies on chemokines and their receptors will not only assist in early diagnosis of gastric cancer, as well as estimation of clinical prognosis, but also provide an intervention target for gastric cancer.
Objective To observe the influence of triamcinolone acetonide (TA) on the expression of pigment epitheliumderived factor (PEDF) of human retinal pigment epithelial (RPE) cells. Methods Cultured humanRPE cells (4th－6th generations) were treated with four different concentrations of TA (40, 400, 4times;103 and 4times;104 mu;g/L) for three different periods (12 or 24 or 48 hours), the levels of PEDF protein in the cell culture supernatant and cell lysates were determined by Western blot. After the initial experiment, RPE cells were treated with or without tumor necrosis factor-alpha; (TNF-alpha;, 20 ng/ml） for 24 hours, followed by TA (400 mu;g/L) treatment. The levels of PEDF and phospho-p38 mitogen activated protein kinase(p-p38MAPK) protein expression in cell culture supernatant and cell lysates were measured by Western blot. Results TAtreated RPE cells had higher PEDF expression, and 400 mu;g/L TA group had the highest effect (F＝16.98,P＜0.05). 400 mu;g/L TA treatment for one, six or 24 hours, with or without TNF-alpha; pretreatment, could all promote the PEDF expression and inhibit the p-p38MAPK protein expression (F＝16.87, 10.28; P＜0.01). TNF-alpha; pretreatment alone could inhibit PEDF protein expression and promote p-p38MAPK protein expression (F=16.87, 10.28; P＜0.01). Conclusions TA can up-regulate the expression of PEDF, and downregulate the expression of p-p38MAPK in the cultured human RPE cells.
Objective To investigate the effects of histone modification on the expression of chemokines in alveolar epithelial typeⅡ cells ( AECⅡ) in a rat model of chronic obstructive pulmonary disease ( COPD) . Methods 20 SD rats were randomly assigned to a normal control group and a COPD group. The rat model of COPD was established by cigarette smoking. Lung histological changes were observed by HE staining. AECⅡ cells were isolated and identified by alkaline phosphatase staining and electron microscopic. The mRNA expressions of monocyte chemoattractant protein ( MCP) -1, IL-8, and macrophage inflammatory protein ( MIP) -2αwere detected by real-time quantitative PCR. The expression of histone deacetylase ( HDAC) 2 was measured by western blot. Chromatin immunoprecipitation ( ChIP) was used todetect H3 and H4 acetylation, and H4K9 methylation in the promoter region of chemokine gene. Results Compared with the control group, the mRNA expressions of MCP-1, IL-8, and MIP-2αin the COPD group increased 4. 48,3. 14, and 2. 83 times, respectively. The expression of HDAC2 protein in the COPD group wassignificantly lower than in the control group ( 0. 25 ±0. 15 vs. 0. 66 ±0. 15, P lt; 0. 05) . The expression of HDAC2 had a negative correlation with the gene expressions of IL-8, MCP-1, and MIP-2α( r = - 0. 960,- 0. 914, - 0. 928, respectively, all P lt;0. 05) . The levels of H3 and H4 acetylation were higher, and H4K9 methylation level was lower in the promoter region of chemokine gene in the COPD group compared with the control group ( all P lt; 0. 05) . Conclusions MCP-1, IL-8, and MIP-2α participate and promote the lung inflammatory response in COPD. HDAC2-mediated histone modification may play an important role in COPD inflammation.
CXC chemokine ligand 12 (CXCL12) is a kind of small molecular polypeptide substance that can move cells towards specific parts. It is widely distributed in heart, skeletal muscle, liver, brain and so on. Current studies believe that CXCL12 plays a role in the formation and progression of cardiovascular diseases by binding to CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), but the mechanism is not very clear, and even some contrary experimental results appear. This review mainly discusses the role of CXCL12-CXCR4/ACKR3 axis in atherosclerosis, myocardial infarction, and myocardial remodeling, in order to explore the inflammatory mechanism in the development of coronary heart disease and provide a basis for further research of clinical drugs.
ObjectiveTo systematically review the relationship between the expression of CXCL12/CXCR4 and pancreatic cancer.MethodsPubMed, EMbase, The Cochrane Library, Wiley Online Library, CNKI, VIP, WanFang Data and CBM databases were electronically searched to collect case-control studies on CXCL12/CXCR4 expression in pancreatic cancer from inception to February 1st 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 21 case-control studies involving 1 677 cases and 1 690 controls were included. The results of meta-analysis showed that the expression of CXCR4 in pancreatic cancer tissue was higher than normal tissue (OR=21.40, 95%CI 5.70 to 80.31, P<0.01), in carcinoma of head of pancreas been higher than carcinoma of pancreatic body and tail, (OR=1.58, 95%CI 1.02 to 2.44, P=0.04), in pancreatic cancer with lymph node metastasis been higher than without lymph node metastasis (OR=3.14, 95%CI 1.98 to 4.99, P<0.01), in pancreatic cancer with high TNM stages (Ⅲ, Ⅳ) been higher than low TNM stages (Ⅰ, Ⅱ) (OR=3.67, 95%CI 1.98 to 6.81, P<0.01), in pancreatic cancer with distant metastasis been higher than without distant metastasis (OR=3.56, 95%CI 1.71 to 7.39, P<0.01), and in pancreatic cancer with vascular invasion was higher than without vascular invasion (OR=3.22, 95%CI 1.70 to 6.09, P<0.01). The expression of CXCR4 was not statistically correlated with age, gender, pancreatic cancer tissue and paracancerous tissue, pancreatic cancer tissue and paracancerous lymph nodes, differentiation degree. There was no statistical correlation between the expression of CXCL12 and the differentiation degree, and lymph node metastasis.ConclusionsIn pancreatic cancer, the high expression of CXCR4 is related to lymph node metastasis, high TNM stage, distant metastasis, vascular invasion indicate poor prognosis. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
Objective To study the expression and significance of CCR chemokine receptor-7 (CCR7) protein and vascular endothelial growth factor-D (VEGF-D) protein in the progression of breast cancer, including normal breast tissue, slight and moderate atypical hyperplasia, severe atypical hyperplasia and intraductal carcinoma in situ, as well as invasive ductal carcinoma. Methods Immunohistochemistry was used to detect the expression of CCR7 and VEGF-D protein in the nomal breast tissue (n=20), slight and moderate ductal atypical hyperplasia tissue (n=20), severe atypical hyperplasia and intraductal carcinoma in situ tissue, as well as invasive ductal breast carcinoma tissue (n=73). In addition, the D2-40 staining was also used to determine lymphatic microvessel density (LMVD). Meanwhile, the relationship between the expression of the two kinds of protein and clinicopathological factors/LMVD was analyzed by statistical analysis in breast cancer, and the correlation between expression of CCR7 protein and expression of VEGF-D protein was analyzed too. Results ①The positive rates of CCR7 protein (χ 2 =23.905，P<0.050) and VEGF-D protein (χ 2 =22.349，P<0.050) were gradually increased in the normal breast tissue group 〔CCR7 protein: 0 (0/20), VEGF-D protein: 5.0% (1/20)〕, slight and moderate atypical hyperplasia group 〔CCR7 protein: 5.0% (1/20), VEGF-D protein: 20.0% (4/20)〕, severe atypical hyperplasia and intraductal carcinoma in situ group 〔CCR7 protein: 30.0% (6/20), VEGF-D protein: 40.0% (8/20)〕, and invasive ductal carcinoma group 〔CCR7 protein: 47.9% (35/73), VEGF-D protein: 57.5% (42/73)〕. ②The LMVD value gradually increased in normal breast tissue group (2.00±1.02), slight and moderate atypical hyperplasia group (6.70± 3.48), severe atypical hyperplasia and intraductal carcinoma in situ group (9.01±2.13), as well as invasive ductal carcinoma group (16.32±4.07), there was significant difference between any 2 groups (P<0.050). ③The expressions of CCR7 protein and VEGF-D protein were correlated with clinical staging, histological grading, lymph node metastasis, and expression of human epidermal growth factor receptor-2 (HER-2) protein in patients with breast cancer (P<0.050), the higher positive rates of CCR7 and VEGF-D protein occurred in patients with higher histological grading, later clinical staging of Ⅲ+Ⅳ (compared with staging of Ⅰ+Ⅱ), lymph node metastasis (compared with no lymph node metastasis), and positive expression of HER-2 protein (compared with negative expression of HER-2 protein). The result indicated that LMVD value was related with expression of VEGF-D protein (r=0.623, P<0.010) in patients with breast cancer, but there was no correlation with expression of CCR7 protein (r=-0.303, P>0.050). Furthermore, there was weak positive correlation between expression of CCR7 protein and expression of VEGF-D protein in breast cancer (r=0.112, P<0.050). Conclusion The results strongly suggest that the expression levels of the VEGF-D protein and CCR7 protein indicate the potential of translation some extent, and they play an important role in the progression of breast cancer.
ObjectiveBased on the rat in situ perfusion system, to explore the effect of up-regulating Chemokine (C-X-C motif) receptor 4 (CXCR4) expression on bone marrow neutrophils in modulating its ECC-related rapid release. MethodsTwelve SD rats were randomly divided into fucoidan perfusion group (F, n=6) and control group (C, n=6) after in situ perfusion system establishment. Rats in F group received perfusion of fucoidan solution (total volume 6 ml, 1 h) and C group received buffer only. Femurs from two groups were dissected after one-hour perfusion and bone marrow tissues were collected. The neutrophil CXCR4 expression in two groups were compared using flowcytometry. Eighteen SD rats were randomly divided into fucoidan perfusion group (F', n=6), fucoidan and AMD-3100 perfusion group (F+AMD3100, n=6) and control group (C', n=6) after in situ perfusion system establishment. Rats received desired interventions before stimulation from ECC plasma. After that, 40-min perfusions of buffer were added and total counts of neutrophil in perfusates were compared. ResultsThe percentages of CXCR4 (+) cell and CXCR4 expression fluorescence in F group were 4.71%±0.21% and 161.3±7.8 respectively while the values were 1.11%±0.11% and 58.4±6.5 respectively in C group. Values in F group were both significantly higher than those in C group (P<0.05). The total counts of neutrophil in perfusates from F' group, F+AMD3100 and C' group were 261 393.7±12 470.6, 872 635.2±10 430.6 and 818 675.2±10 708.8, respectively. Statistically differences were observed between each other (P<0.05). ConclusionBone marrow neutrophil CXCR4 expression of SD rat could be effectively up-regulated by perfusion of fucoidan within the in situ perfusion system. ECC-plasma-stimulated bone marrow neutrophil release in rat could be inhibited by fucoidan induced up-regulation of neutrophil CXCR4 expression, and this inhibition effect could be canceled by AMD-3100 intervention.
Objective The observe the effects of interferon-inducible protein-10 (IP-10) on proliferation, migration and capillary tube formation of human retinal vascular endothelial cells (HREC) and human umbilical vein endothelial cells (HUVEC). Methods The chemokine receptor (CXCR3) mRNA of HREC and HUVEC were quantified by reverse transcriptase polymerase chain reaction (RT-PCR). In the presence of the different concentrations of IP-10, the difference in proliferation capacity of HREC and HUVEC were analyzed by cell counting kit-8 (CCK-8) methods. Wound scratch assay and threedimensional in vitro matrigel assay were used for measuring migration and capillary tube formation of HREC and HUVEC, respectively. Results RT-PCR revealed both HREC and HUVEC expressed CXCR3. The proliferation of HREC in the presence of IP-10 was inhibited in a dosagedependent manner (F=6.202,P＜0.05), while IP-10 showed no effect on the inhibitory rate of proliferation of HUVEC (F=1.183,P＞0.05). Wound scratch assay showed a significant reduction in the migrated distance of HREC and HUVEC under 10 ng/ml or 100 ng/ml IP-10 stimulation (F=25.373, 23.858; P＜0.05). There was no effect on the number of intact tubules formed by HREC in the presence of 10 ng/ml or 100 ng/ml IP-10. The number of intact tubules formed by HREC in the presence of 1000 ng/ml IP-10 was remarkably smaller. The difference of number of intact tubules formed by HREC among 10, 100, 1000 ng/ml IP-10 and nonintervention group was statistically significant (F=5.359,P＜0.05). Conclusion IP-10 can inhibit the proliferation, migration and capillary tube formation ability of HREC and the migration of HUVEC.
ObjectiveTo investigate the relationship between the pathological and functional changes of the retina and the expression of monocyte chemoattractant protein (MCP)-1 after retinal laser injury in mice. MethodsA total of 116 C57BL/6 mice were randomly divided into the normal group (58 mice) and the injured group (58 mice). Retinal laser injuries were induced by Argon ion laser. At 1, 3, 7 days after laser injury, electroretinogram (ERG) responses were recorded to detect the function of the retina. Hematoxylin and eosin (HE) staining was performed to observe pathological changes. Quantitative real-time polymerase chain reaction (PCR) was performed to detect gene expression of MCP-1. Western blot was used to measure the protein expression of MCP-1. ResultsHE staining showed a progressive damage of the retinal structure. The results of ERG showed that the differences of dark-adaptive a wave (t=6.998, 9.594, 13.778) and b wave (t=12.089, 13.310, 21.989) amplitudes of 1, 3 and 7 day post-injury between normal group and injured group were statistically significant (P=0.000). At 1 day post-injury, the differences of light adaptive b wave amplitudes between the two groups were statistically significant (t=8.844, P=0.000). While the differences of light-adaptive a wave amplitudes were not (t=2.659,P=0.200). At 3, 7 days post-injury, the differences of a (t=3.076, 7.544) and b wave amplitudes (t=10.418, 8.485) between the two groups were statistically significant (P=0.000). In dark-adaptive ERG, the differences of a wave amplitudes between 1 day and 3 days (t=3.773), 1 day and 7 days (t=5.070) and b wave amplitudes between 1 day and 7 days (t=4.762) were statistically significant (P<0.01), while the differences of a wave amplitudes between the 3 days and 7 days (t=1.297) and b wave amplitudes between 1 day and 3 days (t=2.236), 3 day and 7 days (t=2.526) were not significant (P=0.660, 0.120, 0.060). In light-adaptive ERG, the differences of a wave amplitudes between 1 day and 7 days (t=2.992) and b wave amplitudes between 1 day and 3 days (t=3.570), 1day and 7 days (t=4.989) were statistically significant (P<0.05), while the differences of a wave amplitudes between 1 day and 3 days (t=0.516), the 3 days and 7 days (t=2.475) and b wave amplitudes between 3 days and 7 days (t=1.419) were not significant (P=1.000, 0.710, 0.070). Quantitative real-time PCR showed that the differences of MCP-1 gene expression at 1, 3 and 7 day post-injury between normal group and injured group were statistically significant (t=14.329, 16.861, 5.743; P<0.05). Western blot showed that the differences of MCP-1 protein expression at 1, 3 and 7 day post-injury between normal group and injured group were statistically significant (t=75.068, 54.145, 14.653; P<0.05). ConclusionIn the first 7 days after mice retinal laser injury, there are progressive pathological and functional damage of the retina, which might be correlated with MCP-1 expression.
Objective To summarize the relationships between chemokines or chemokine receptors, especially CCL19/CCL21-CCR7 and CXCL12-CXCR4 axis and occurrence and development of gastric cancer. Methods Domestic and international publications online involving the relationships between chemokines, chemokine recepotors and gastric cancer in recent years were collected and reviewed. Results By regulating the microenvironment of the growth of gastric cancer, CCL19/CCL21-CCR7 played an important role in lymph node metastasis and CXCL12-CXCR4 axis played a key role in the development of peritoneal carcinomatosis. CCR7 might function as a specific prognostic marker for lymph node metastasis of gastric cancer. Blocking the CXCL12-CXCR4 axis might be useful for the future development of a more effective therapeutic strategy for gastric cancer involved in peritoneal dissemination. Conclusions Chemokines and chemokine receptors promote the evolution of gastric cancer in variable ways, so the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment. As new therapeutic targets, chemokines and chemokine receptors have a prosperity for the clinic evaluation and treatment of gastric cancer.