Summary: In order to explore the possible role of CC chemokine ligand 20 (CCL20) and its receptor CC chemokine receptor 6 (CCR6) in the pathogenesis of psoriasis, the expression levels of mRNA of them in psoriatic les...Summary: In order to explore the possible role of CC chemokine ligand 20 (CCL20) and its receptor CC chemokine receptor 6 (CCR6) in the pathogenesis of psoriasis, the expression levels of mRNA of them in psoriatic lesions were investigated. The skin biopsies were collected from skin lesions in 35 cases of psoriasis vulgaris and 18 normal controls. RT-PCR was used to semi-quantitatively analyze the mRNA expression of CCL20 and CCR6 in the psoriatic lesions and the normal skin tissues. The results showed that the mRNA of CCL20 and CCR6 was present in every specimen. The expression levels of CCL20 mRNA in skin lesions were 1.1397±0.0521, which were greatly higher than those in normal controls (0.8681±0.0308) (P<0.001). The expression levels of CCR6 mRNA in skin lesions were 1.1103±0.0538, significantly higher than in the controls (0.9131±0.0433, P<0.001). These findings indicate that up-regulated expression of CCL20 and CCR6 mRNA might be related to the pathogenesis of psoriasis.展开更多
Objective: The aim of this study was to analyze the expression of CC chemokine receptor 7 (CCR7) in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer (NSCLC), explore the relations...Objective: The aim of this study was to analyze the expression of CC chemokine receptor 7 (CCR7) in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer (NSCLC), explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods: SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field (x 400) of microscope by double blind method. Results: (1) The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue (P 〈 0.005); (2) The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences (P = 0.177); (3) The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group (P = 0.016); (4) Along with the increment of clinical stage, the CCR7 expression had a tendency to increase (P = 0.003). Conclusion: CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.展开更多
Objectives: Monocytes/macrophages accumulate in the synovial membrane in rheumatoid arthritis and play a key role in disease pathogenesis, contributing to inflammation, cartilage destruction and bone erosion. Identifi...Objectives: Monocytes/macrophages accumulate in the synovial membrane in rheumatoid arthritis and play a key role in disease pathogenesis, contributing to inflammation, cartilage destruction and bone erosion. Identification of molecules involved in monocyte/macrophage recruitment in inflammation is crucial for development of therapeutic interventions. Chemokine receptor CCR9 is up-regulated on these cells in peripheral blood and synovium of rheumatoid patients. This study investigated the course of antigen-induced arthritis in CCR9 deficient C57BL/6 mice in comparison to wild type animals to determine whether CCR9 is critical for disease severity and progression. Methods: Methylated bovine serum albumin was used for induction of uni-lateral arthritis by direct injection into the knee joints of preimmunized animals. Arthritis is confined to the injected joint allowing comparison with the normal opposing joint. Clinical severity of arthritis was assessed by measuring swelling in the arthritic joint in comparison to the normal joint. Histological analysis was performed to assess the extent of leukocyte infiltration and cartilage depletion. Results: Levels of swelling were not significantly different between wild type and CCR9 deficient mice. Similarly there was no significant difference in histological severity of arthritis when comparing CCR9-deficient mice to wild type mice. Conclusions: CCR9 was not required for development of synovial inflammation and cartilage destruction in the anti-gen-induced model of arthritis in C57BL/6 mice in this study. This may reflect a true lack of a pathogenic role of CCR9 on monocyte/macrophage function in vivo or it may reflect differences in the current antigen-induced arthritis model when compared to human RA.展开更多
Chemokines belong to a superfamily of small, cytokinelike proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction w...Chemokines belong to a superfamily of small, cytokinelike proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20(CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer(CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.展开更多
BACKGROUND Acute pancreatitis(AP)is an inflammatory disease,which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal.The 2012 Atlanta classification s...BACKGROUND Acute pancreatitis(AP)is an inflammatory disease,which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal.The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely,mild AP(MAP),moderately severe AP(MSAP),and severe AP(SAP).Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial.AIM To identify the role of the chemokine receptor 8(CCR8),expressed by T-helper type-2 Lymphocytes and peritoneal macrophages,and its possible association to Interleukin(IL)-6 and AP stratification.METHODS This study was a prospective case-control study.A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital.Bioassays were performed on 29 patients(14 MAP,11 MSAP,and 4 SAP)and 6 healthy controls as part of a preliminary study.A total of 12 mL of blood samples were collected at Day(D)1,3,5,and 7 post epigastric pain.Using multiplex immunoassay panels,real-time polymerase chain reaction(qRT-PCR)arrays,and multicolour flow cytometry analysis,immune response-related proteins,genes,and cells were profiled respectively.GraphPad Prism^(TM) software and fold change(FC)analysis was used to determine differences between the groups.P<0.05 was considered significant.RESULTS The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P=0.001 and P=0.013 respectively,in a multiplex assay.When a FC of 2 was applied to identify differentially expressed genes using RT2 Profiler,CCR8 was shown to increase steadily with disease severity from MAP(1.33),MSAP(38.28)to SAP(1172.45)median FC.Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log10,compared to healthy control respectively at D3.The findings also showed differing lymphocyte and monocyte cell frequency between the groups.With monocyte population frequency as high as 70%in MSAP at D3.CONCLUSION The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.展开更多
目的:观察凉血解毒汤对银屑病小鼠皮肤组织中CC趋化因子配体20(CCL20)/CC趋化因子受体6(CCR6)表达的干预作用。方法:24只BALB/c雄性小鼠随机分为空白对照组、银屑病模型组、凉血解毒汤中药治疗组和趋化因子CCL20单克隆抗体(阳性药)治疗...目的:观察凉血解毒汤对银屑病小鼠皮肤组织中CC趋化因子配体20(CCL20)/CC趋化因子受体6(CCR6)表达的干预作用。方法:24只BALB/c雄性小鼠随机分为空白对照组、银屑病模型组、凉血解毒汤中药治疗组和趋化因子CCL20单克隆抗体(阳性药)治疗组。用咪喹莫特诱导小鼠银屑病模型,采用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准观察银屑病样小鼠皮损的变化情况。光镜下观察皮损组织形态学变化,测量表皮层厚度。采用real-time PCR检小鼠皮肤组织样本中CCL20和CCR6表达的变化。结果:银屑病模型组小鼠皮肤出现大量鳞屑和红斑,表皮增厚;与银屑病模型组小鼠比较,凉血解毒汤组小鼠银屑病样皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。趋化因子CCL20单克隆抗体治疗组小鼠银屑病皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。结论:凉血解毒汤可能通过下调CCL20/CCR6的表达来减轻银屑病小鼠的皮肤病变。展开更多
目的:探讨人趋化因子受体6(CCR6)及其配体CCL20的表达与结肠癌肝转移的关系。方法:选择2012年10月-2014年10月在本院行结肠癌根治术的患者93例作为研究对象,采用实时荧光定量PCR检测93例患者的结肠癌组织、正常肠黏膜组织及其中14例结...目的:探讨人趋化因子受体6(CCR6)及其配体CCL20的表达与结肠癌肝转移的关系。方法:选择2012年10月-2014年10月在本院行结肠癌根治术的患者93例作为研究对象,采用实时荧光定量PCR检测93例患者的结肠癌组织、正常肠黏膜组织及其中14例结肠癌肝转移组织、肝转移灶旁肝组织中CCL20及CCR6 m RNA表达情况,分析比较其差异。结果:CCR6及CCL20 m RNA在结肠癌和肝转移灶中高表达,并且均显著高于癌旁组织,比较差异有统计学意义(P<0.05)。结肠癌组织中CCR6及CCL20 m RNA表达与患者的性别、年龄、肿瘤大小及组织学类型无明显关系(P>0.05),与TNM分期有关(P<0.05)。结论:CCR6及其配体CCL20可能参与调节结肠癌向肝脏特异性转移过程。展开更多
目的探讨冠心病患者趋化因子配体20(CCL20)、趋化因子受体6(CCR6)和白介素-17(IL-17)的表达与预后的关系。方法选择2016年7月至11月温州医科大学附属第一医院心内科收治的急性心肌梗死(AMI)患者96例,稳定型心绞痛(SAP)患者45例,无冠心...目的探讨冠心病患者趋化因子配体20(CCL20)、趋化因子受体6(CCR6)和白介素-17(IL-17)的表达与预后的关系。方法选择2016年7月至11月温州医科大学附属第一医院心内科收治的急性心肌梗死(AMI)患者96例,稳定型心绞痛(SAP)患者45例,无冠心病患者65例。采用酶联免疫吸附法检测血浆CCL20和IL-17水平。实时定量PCR检测单核细胞中CCR6 m RNA水平。采用logistic回归分析确定冠心病的危险因素。Gensini评分评价冠状动脉狭窄程度,分析CCL20、CCR6和IL-17与Gensini评分的相关性。对AMI患者进行随访以观察主要不良心血管事件(MACE)风险。结果AMI组和SAP组患者血浆CCL20和IL-17水平、外周血单核细胞CCR6 m RNA表达水平均显著高于对照组(均P<0.01)。多因素分析显示,CCL20和IL-17是冠心病发生的独立危险因素(均P<0.01)。CCR6 m RNA、CCL20和IL-17水平均与Gensini评分呈正相关(r=0.32、0.65、0.56,均P<0.01)。随访期间CCL20表达水平较高的AMI者MACE发生率较高。结论冠心病患者CCL20和IL-17增高,CCL20与AMI患者预后相关。展开更多
文摘Summary: In order to explore the possible role of CC chemokine ligand 20 (CCL20) and its receptor CC chemokine receptor 6 (CCR6) in the pathogenesis of psoriasis, the expression levels of mRNA of them in psoriatic lesions were investigated. The skin biopsies were collected from skin lesions in 35 cases of psoriasis vulgaris and 18 normal controls. RT-PCR was used to semi-quantitatively analyze the mRNA expression of CCL20 and CCR6 in the psoriatic lesions and the normal skin tissues. The results showed that the mRNA of CCL20 and CCR6 was present in every specimen. The expression levels of CCL20 mRNA in skin lesions were 1.1397±0.0521, which were greatly higher than those in normal controls (0.8681±0.0308) (P<0.001). The expression levels of CCR6 mRNA in skin lesions were 1.1103±0.0538, significantly higher than in the controls (0.9131±0.0433, P<0.001). These findings indicate that up-regulated expression of CCL20 and CCR6 mRNA might be related to the pathogenesis of psoriasis.
文摘Objective: The aim of this study was to analyze the expression of CC chemokine receptor 7 (CCR7) in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer (NSCLC), explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods: SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field (x 400) of microscope by double blind method. Results: (1) The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue (P 〈 0.005); (2) The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences (P = 0.177); (3) The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group (P = 0.016); (4) Along with the increment of clinical stage, the CCR7 expression had a tendency to increase (P = 0.003). Conclusion: CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.
文摘Objectives: Monocytes/macrophages accumulate in the synovial membrane in rheumatoid arthritis and play a key role in disease pathogenesis, contributing to inflammation, cartilage destruction and bone erosion. Identification of molecules involved in monocyte/macrophage recruitment in inflammation is crucial for development of therapeutic interventions. Chemokine receptor CCR9 is up-regulated on these cells in peripheral blood and synovium of rheumatoid patients. This study investigated the course of antigen-induced arthritis in CCR9 deficient C57BL/6 mice in comparison to wild type animals to determine whether CCR9 is critical for disease severity and progression. Methods: Methylated bovine serum albumin was used for induction of uni-lateral arthritis by direct injection into the knee joints of preimmunized animals. Arthritis is confined to the injected joint allowing comparison with the normal opposing joint. Clinical severity of arthritis was assessed by measuring swelling in the arthritic joint in comparison to the normal joint. Histological analysis was performed to assess the extent of leukocyte infiltration and cartilage depletion. Results: Levels of swelling were not significantly different between wild type and CCR9 deficient mice. Similarly there was no significant difference in histological severity of arthritis when comparing CCR9-deficient mice to wild type mice. Conclusions: CCR9 was not required for development of synovial inflammation and cartilage destruction in the anti-gen-induced model of arthritis in C57BL/6 mice in this study. This may reflect a true lack of a pathogenic role of CCR9 on monocyte/macrophage function in vivo or it may reflect differences in the current antigen-induced arthritis model when compared to human RA.
文摘Chemokines belong to a superfamily of small, cytokinelike proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20(CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer(CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.
基金Supported by the South African National Research Foundation,No.121277the University of the Witwatersrand Individual Research,No.001283844110151211055142the Faculty of Health Sciences,University of the Witwatersrand Seed Funding,No.0012518441101512110500000000000000004550.
文摘BACKGROUND Acute pancreatitis(AP)is an inflammatory disease,which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal.The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely,mild AP(MAP),moderately severe AP(MSAP),and severe AP(SAP).Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial.AIM To identify the role of the chemokine receptor 8(CCR8),expressed by T-helper type-2 Lymphocytes and peritoneal macrophages,and its possible association to Interleukin(IL)-6 and AP stratification.METHODS This study was a prospective case-control study.A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital.Bioassays were performed on 29 patients(14 MAP,11 MSAP,and 4 SAP)and 6 healthy controls as part of a preliminary study.A total of 12 mL of blood samples were collected at Day(D)1,3,5,and 7 post epigastric pain.Using multiplex immunoassay panels,real-time polymerase chain reaction(qRT-PCR)arrays,and multicolour flow cytometry analysis,immune response-related proteins,genes,and cells were profiled respectively.GraphPad Prism^(TM) software and fold change(FC)analysis was used to determine differences between the groups.P<0.05 was considered significant.RESULTS The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P=0.001 and P=0.013 respectively,in a multiplex assay.When a FC of 2 was applied to identify differentially expressed genes using RT2 Profiler,CCR8 was shown to increase steadily with disease severity from MAP(1.33),MSAP(38.28)to SAP(1172.45)median FC.Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log10,compared to healthy control respectively at D3.The findings also showed differing lymphocyte and monocyte cell frequency between the groups.With monocyte population frequency as high as 70%in MSAP at D3.CONCLUSION The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.
文摘目的:观察凉血解毒汤对银屑病小鼠皮肤组织中CC趋化因子配体20(CCL20)/CC趋化因子受体6(CCR6)表达的干预作用。方法:24只BALB/c雄性小鼠随机分为空白对照组、银屑病模型组、凉血解毒汤中药治疗组和趋化因子CCL20单克隆抗体(阳性药)治疗组。用咪喹莫特诱导小鼠银屑病模型,采用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准观察银屑病样小鼠皮损的变化情况。光镜下观察皮损组织形态学变化,测量表皮层厚度。采用real-time PCR检小鼠皮肤组织样本中CCL20和CCR6表达的变化。结果:银屑病模型组小鼠皮肤出现大量鳞屑和红斑,表皮增厚;与银屑病模型组小鼠比较,凉血解毒汤组小鼠银屑病样皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。趋化因子CCL20单克隆抗体治疗组小鼠银屑病皮损程度较轻,红斑、鳞屑以及表皮增厚程度轻于模型组,PASI分数降低,皮肤组织CCL20以及CCR6的表达明显低于模型组。结论:凉血解毒汤可能通过下调CCL20/CCR6的表达来减轻银屑病小鼠的皮肤病变。
文摘目的:探讨人趋化因子受体6(CCR6)及其配体CCL20的表达与结肠癌肝转移的关系。方法:选择2012年10月-2014年10月在本院行结肠癌根治术的患者93例作为研究对象,采用实时荧光定量PCR检测93例患者的结肠癌组织、正常肠黏膜组织及其中14例结肠癌肝转移组织、肝转移灶旁肝组织中CCL20及CCR6 m RNA表达情况,分析比较其差异。结果:CCR6及CCL20 m RNA在结肠癌和肝转移灶中高表达,并且均显著高于癌旁组织,比较差异有统计学意义(P<0.05)。结肠癌组织中CCR6及CCL20 m RNA表达与患者的性别、年龄、肿瘤大小及组织学类型无明显关系(P>0.05),与TNM分期有关(P<0.05)。结论:CCR6及其配体CCL20可能参与调节结肠癌向肝脏特异性转移过程。
文摘目的探讨冠心病患者趋化因子配体20(CCL20)、趋化因子受体6(CCR6)和白介素-17(IL-17)的表达与预后的关系。方法选择2016年7月至11月温州医科大学附属第一医院心内科收治的急性心肌梗死(AMI)患者96例,稳定型心绞痛(SAP)患者45例,无冠心病患者65例。采用酶联免疫吸附法检测血浆CCL20和IL-17水平。实时定量PCR检测单核细胞中CCR6 m RNA水平。采用logistic回归分析确定冠心病的危险因素。Gensini评分评价冠状动脉狭窄程度,分析CCL20、CCR6和IL-17与Gensini评分的相关性。对AMI患者进行随访以观察主要不良心血管事件(MACE)风险。结果AMI组和SAP组患者血浆CCL20和IL-17水平、外周血单核细胞CCR6 m RNA表达水平均显著高于对照组(均P<0.01)。多因素分析显示,CCL20和IL-17是冠心病发生的独立危险因素(均P<0.01)。CCR6 m RNA、CCL20和IL-17水平均与Gensini评分呈正相关(r=0.32、0.65、0.56,均P<0.01)。随访期间CCL20表达水平较高的AMI者MACE发生率较高。结论冠心病患者CCL20和IL-17增高,CCL20与AMI患者预后相关。