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
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
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
Purpose: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer invasion and metastasis. This study was aimed to investigate CCR7 and CXCR4 expressions and evaluate the association ...Purpose: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer invasion and metastasis. This study was aimed to investigate CCR7 and CXCR4 expressions and evaluate the association between their expressions and the clinicopathological features in gastrointestinal cancer. Method: 27 paired tissue samples from patients who had curative surgery for gastrointestinal cancer were obtained. Quantitative real-time PCR, immunochemistry assay and western blot analysis were carried out to investigate the expressions of CCR7, CXCR4 expressions in gastrointestinal cancer. Results: The cancer tissues expressed significant higher level of CCR7 (P = 0.000) and CXCR4 (P = 0.000) protein than the adjacent normal mucosa. Expressions of CCR7 (P = 0.002) and CXCR4 (P = 0.003) protein in cancer tissues exhibited significant correlation with differentiation in gastrointestinal cancer. Conclusion: Expressions of CCR7 and CXCR4 protein were associated with differentiation in gastrointestinal cancer. CCR7 and CXCR4 may be predictive factors for poor prognosis in patients with gastrointestinal cancer.展开更多
Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy,largely due to limited T cell infiltration in the tumors.Here,we show that mice bearing intracranial tumors exhibit systemic immun...Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy,largely due to limited T cell infiltration in the tumors.Here,we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow,leading to reduced T cell infiltration in brain tumors.Elevated plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing mice.Immunosuppression mediated by glucocorticoid-induced T cell dynamics and the subsequent tumor growth promotion can be abrogated by adrenalectomy,the administration of glucocorticoid activation inhibitors or glucocorticoid receptor antagonists,and in mice with T cell-specific deletion of glucocorticoid receptor.CCR8 expression in T cells is increased in tumor-bearing mice in a glucocorticoid receptor-dependent manner.Additionally,chemokines CCL1 and CCL8,the ligands for CCR8,are highly expressed in bone marrow immune cells in tumor-bearing mice to recruit T cells.These findings suggested that brain tumor-induced glucocorticoid surge and CCR8 upregulation in T cells lead to T cell sequestration in bone marrow,impairing the anti-tumor immune response.Targeting the glucocorticoid receptor-CCR8 axis may offer a promising immunotherapeutic approach for the treatment of intracranial tumors.展开更多
Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comp...Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comprised of 1251 subjects(915 men and 336 women)aged 15 -80 years and none was HIV-1 positive.Genotyping of allelic CCR5-△32,CCR2-641 and SDF1-3' A variants was performed using PCR or PCR/RFLP assay,and further confirmed by direct DNA sequencing.Results Our finding shows that the△32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119(n= 1254).The frequencies of mutant CCR2-641 and SDF1-3'A alleles were 0.20023(n = 1251)and 0.2873(n = 893),in this population,which are higher than those found in American Caucasians.Furthermore the polymorphisms of CCR2-641 and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians.Statistical analysis showed that the genotype distribution of CCR5-△32,CCR2-641 and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation.Conclusion The CCR5-△32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese.The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791)in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.展开更多
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.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
文摘Purpose: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer invasion and metastasis. This study was aimed to investigate CCR7 and CXCR4 expressions and evaluate the association between their expressions and the clinicopathological features in gastrointestinal cancer. Method: 27 paired tissue samples from patients who had curative surgery for gastrointestinal cancer were obtained. Quantitative real-time PCR, immunochemistry assay and western blot analysis were carried out to investigate the expressions of CCR7, CXCR4 expressions in gastrointestinal cancer. Results: The cancer tissues expressed significant higher level of CCR7 (P = 0.000) and CXCR4 (P = 0.000) protein than the adjacent normal mucosa. Expressions of CCR7 (P = 0.002) and CXCR4 (P = 0.003) protein in cancer tissues exhibited significant correlation with differentiation in gastrointestinal cancer. Conclusion: Expressions of CCR7 and CXCR4 protein were associated with differentiation in gastrointestinal cancer. CCR7 and CXCR4 may be predictive factors for poor prognosis in patients with gastrointestinal cancer.
基金supported by grants from the National Key R&D Program of China(2022YFA0807300 and 2021YFA1100600)the National Natural Science Foundation of China(81930085 and 32150710523)the Jiangsu Province International Joint Laboratory for Regenerative Medicine Fund and Suzhou Science and Technology Bureau(ZXL2021440,SWY202202 and SYS2020087).
文摘Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy,largely due to limited T cell infiltration in the tumors.Here,we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow,leading to reduced T cell infiltration in brain tumors.Elevated plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing mice.Immunosuppression mediated by glucocorticoid-induced T cell dynamics and the subsequent tumor growth promotion can be abrogated by adrenalectomy,the administration of glucocorticoid activation inhibitors or glucocorticoid receptor antagonists,and in mice with T cell-specific deletion of glucocorticoid receptor.CCR8 expression in T cells is increased in tumor-bearing mice in a glucocorticoid receptor-dependent manner.Additionally,chemokines CCL1 and CCL8,the ligands for CCR8,are highly expressed in bone marrow immune cells in tumor-bearing mice to recruit T cells.These findings suggested that brain tumor-induced glucocorticoid surge and CCR8 upregulation in T cells lead to T cell sequestration in bone marrow,impairing the anti-tumor immune response.Targeting the glucocorticoid receptor-CCR8 axis may offer a promising immunotherapeutic approach for the treatment of intracranial tumors.
基金ThisprojectwassupportedbyagrantfromNationalNaturalSciencesFoundationofthePRChina (No 3 9770 683 )
文摘Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comprised of 1251 subjects(915 men and 336 women)aged 15 -80 years and none was HIV-1 positive.Genotyping of allelic CCR5-△32,CCR2-641 and SDF1-3' A variants was performed using PCR or PCR/RFLP assay,and further confirmed by direct DNA sequencing.Results Our finding shows that the△32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119(n= 1254).The frequencies of mutant CCR2-641 and SDF1-3'A alleles were 0.20023(n = 1251)and 0.2873(n = 893),in this population,which are higher than those found in American Caucasians.Furthermore the polymorphisms of CCR2-641 and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians.Statistical analysis showed that the genotype distribution of CCR5-△32,CCR2-641 and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation.Conclusion The CCR5-△32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese.The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791)in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.
