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CXC chemokine receptor 3 MODULATES BLEOMYCIN-INDUCED PULMONARY INJURY VIA INVOLVING INFLAMMATORY PROCESS

Chinese Medical Sciences Journal 2006年第3期21卷 152-156页

作者： Jin-ming Gao Bao Lu Zi-jian Guo Department of Respiratory Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100730 Ina Sue Perlmutter Laboratory Division of Pulmonary Children＇s Hospital Department of Medicine Harvard Medical School Boston MA 02115

Objeelive To investigate the role of CXC chemokine receptor 3 （ CXCR3 ） in bleomycin-induced lung injury by using CXCR3 gene deficient mice. Methods Sex-, age-, and weight-matched C57BL/6 CXCR3 gene knockout mice and C57BL/6 wide type mice were challenged by injection of bleomycin via trachea. Lung tissue was stained with HE method. Airway resistance was measured. Bronchoalveolar lavage （BAL） was performed using phosphate buffered saline twice, cell number and differentials were counted by Diff-Quick staining. Interleukin （IL）-4, IL-5, IL-12p40, and interfon-~ in BAL fluid and lung homogenate were measured by enzyme-linked immunosorbent assay. Unpaired t test was explored to compare the difference between two groups. Results On day 7 after bleomycin injection via trachea, CXCR3 knockout mice were protected from bleomycininduced lung injury as evidenced by fewer accumulation of inflammatory cells in the airway and lung interstitium compared with their wild type littermates （ P 〈 0. 05 ）. Airway resistance was also lower in CXCR3 knockout mice compared with wild type mice （P 〈 0. 01 ）. Significantly lower level of inflammatory cytokines release, including the altered production of IL-4 and IL-5 both in BAL fluid and lung tissue was seen in CXCR3 knockout mice than in wild type mice （both P 〈0. 05）. Conclusion CXCR3 signaling promotes inflammatory cells recruiting and initiates inflammatory cytokines cascade following endotracheal bleomycin administration, indicating that CXCR3 might be a therapeutic target for pulmonary injury.

关键词： chemokine receptor bleomycin lung injury inflammation

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Distinct Effect of CD40 and TNF-Signaling on the chemokine/chemokine receptor Expression and Function of the Human Monocyte-Derived Dendritic Cells

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Cellular & Molecular Immunology 2008年第2期5卷 121-131页

作者： Yu Xia Jun Dai Peirong Lu Yong Huang Yipei Zhu Xueguang Zhang Medical Biotechnology Institute Soochow University Suzhou 215007China Department of Immunology Soochow University Suzhou 215007 China Clinic Immunology Laboratory of Jiangsu Province The First Affiliated Hospital of Soochow University Suzhou 215006 China These authors contributed equally to this work

A key and limiting step in the process of human monocyte-derived dendritic cells （mDCs） for clinical use is their in vitro maturation and in vivo migration. We previously observed that CD40 signal facilitated human mDC growth and maturation. To further explore this process, mDCs generated with GM-CSF and IL-4 were co-cultured with apoptotic tumor cells for 24 hours, followed by incubating with anti-CD40 monoclonal antibody or TNF-a for 48 hours to generate mature DCs. The chemokine/chemokine receptor expression and functions of mature DCs upon various stimuli were determined. The expression of costimulatory molecules on apoptotic tumor cell-loaded mature DCs co-cultured with either anti-CD40 antibody （anti-CD40-DCs） or TNF-a （TNF-DCs） were up-regulated compared to immature DCs, consistent with the abilities of these cytokine to drive DC maturation in vitro. The mRNA levels of chemokines such as stromal cell-derived factor-1a （SDF-1a）, EBV-induced molecule 1 ligand chemokine （ELC）, and IFN inducible protein-10 （IP-10） in anti-CD40 activated DCs were increased and the dendritic cell-specific chemokine 1 （DC-CK1） was moderately up-regulated as compared with other mature DCs. The corresponding chemokine receptors CXCR4 and CCR7 of anti-CD40-DCs were significantly expressed. The CXCR3 expression on activated T cells stimulated by anti-CD40-DCs was also increased. Moreover, the anti-CD40-DCs had a stronger ability to stimulate T cell proliferation than any other DCs. The NF-xB activity was much higher in anti-CD40-DCs than that of TNF-DCs. These results offer further evidence of the importance of the CD40 signal in developing efficient human DC vaccines for cancer immune therapy. Cellular ＆ Molecular Immunology.

关键词： dendritic cell chemokine chemokine receptor CD40 CD40 ligand

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Expressions of chemokine receptor CXCR4 and its ligand CXCL12 in salivary adenoid cystic carcinoma

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Journal of Medical Colleges of PLA(China) 2004年第4期19卷 225-228页

作者：徐晓刚吕春堂周中华 Department of Stomatology Changhai Hospital Second Military Medical University Shanghai 200433 China

Objective: To examine expressions of chemokine receptor CXCR4 and its ligand CXCL12 in primary focus and lymphogenous metastasis of salivary adenoid cystic carcinoma (ACC) with lung metastasis. Methods: Using immunohistochemical hypersensitivity catalyzed signal amplification (CSA), expressions of chemokine receptor CXCR4 and ligand CXCL12 were detected in tissue specimens from 20 cases of primary cancer focus and lymphogenous metastasis of salivary adenoid cystic carcinoma, of which 7 cases were associated with lung metastasis and 3 with lympogenous metastasis. Twenty cases of tongue carcinoma (including 10 cases with lymphogenous metastasis) and 15 cases of mucoepidermoid carcinoma (including 5 cases with lymphogenous metastasis) were used as the malignant control group;and salivary mixed tumor (n=10), tongue leukoceratosis (n=10) and cervical lymph node reactive hyperplasia (n=10) were used as the benign control group. Results: Expression of CXCR4 in the tissues and lymph metastases of oral and maxillofacial salivary ACC, mucoepidermoid carcinoma and tongue carcinoma was significantly higher than that of the benign control group (Pchemokine receptor CXCR4 and its ligand CXCL12 may be associated with local invasion and lymphogenous metastasis of oral and maxillofacial cancer, especially with lung metastasis of salivary ACC.

关键词： salivary gland adenoid cystic carcinoma metastasis chemokine receptor chemokine immunohistochemistry

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CXC chemokines and chemokine receptors in gastric cancer: From basic findings towards therapeutic targeting

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World Journal of Gastroenterology 2014年第7期20卷 1681-1693页

作者： Hyo Jin Lee Ik-Chan Song Hwan-Jung Yun Deog-Yeon Jo Samyong Kim Division of Hematology/Oncology Department of Internal MedicineSchool of Medicine Chungnam National University and Chungnam National University HospitalDaejeon 301-721South Korea Cancer Research Institute Chungnam National UniversityDaejeon 301-721South Korea Division of Hematology/Oncology Department of Internal MedicineChungnam National University HospitalDaejeon 301-721South Korea

Gastric cancer is the fourth most common cancer,and the second-highest cause of cancer-related deaths *** extensive research to identify novel diagnostic and therapeutic agents,patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis,and treatment is dependent mainly on conventional cytotoxic *** improve the quality of life and survival of gastric cancer patients,a better understanding of the underlying molecular pathologies,and their application towards the development of novel targeted therapies,is urgently *** are a group of small proteins associated with cytoskeletal rearrangements,the directional migration of several cell types during development and physiology,and the host immune response via interactions with G-protein coupled *** is also growing evidence to suggest that chemokines not only play a role in the immune system,but are also involved in the development and progression of *** gastric cancer,CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor *** chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation,survival,growth,invasion and metastasis,as well as indirectly by regulating angiogenesis,and tumor-leukocyte *** this review,we will focus on the roles of CXC chemokines and their receptors in the development,progression,and metastasis of gastric tumors,and discuss their therapeutic potential for gastric cancer.

关键词： chemokine chemokine receptor Gastric neoplasm Therapeutic target

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chemokine-mimetic plerixafor derivative for tumorspecific delivery of nanomaterials

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Nano Research 2018年第4期11卷 2159-2172页

作者： Seungbeom Ko Gayong Shim Jinyoung Kim Yu-Kyoung Oh College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University 1 Kwanak-ro Kwanak-gu Seoul 08826 Republic of Korea

Here, we report that chemokine-mimetic plerixafor derivatives could govern tumor-specific delivery and functional effects of nanomaterials. Reduced graphene oxide （rGO） nanosheets were used as a model functional nanomaterial, and plerixafor-conjugated lipid （PL/rGO） or a benzylcyclam derivative of plerixafor- conjugated lipid （BPL/rGO） was physically adsorbed onto the surface of rGO. The cellular uptake of surface-modified rGO was dependent on overexpression of the CXCR4 chemokine receptor on cancer cells. In KB cells, the binding affinity of BPL/rGO for CXCR4 was 6.8-fold greater than that of PL/rGO. Notably, cellular uptake patterns correlated with in vitro photothermal anticancer efficacy. The tumor distribution of BPL/rGO was higher than that of PL/rGO and plain rGO in mice bearing CXCR4-overexpressing tumors, whereas the distribution of the various rGO forms was similar in mice harboring CXCR4-negative tumors. Moreover, complete photothermal tumor ablation was observed in BPL/rGO- treated mice bearing CXCR4-positive KB cell tumors, but not in CXCR4-negative MCF-7 cell tumors. These results provide evidence that BPL can be used to enhance the delivery of nanomaterials to CXCR4-overexpressing tumors. chemokine-mimetic BPL can be further applied for nanomaterial-based delivery of photosensitizers, anticancer drugs, or diagnostic tumor imaging agents in CXCR4-overexpressing cancer patients.

关键词： chemokine-mimetic plerixafor derivatives chemokine receptor nanomaterial photothermal therapy

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PEG10 Activation by Co-Stimulation of CXCR5 and CCR7 Essentially Contributes to Resistance to Apoptosis in CD19^(+)CD34^(+) B Cells from Patients with B Cell Lineage Acute and Chronic Lymphocytic Leukemia

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Cellular & Molecular Immunology 2004年第4期1卷 280-294页

作者： ChunsongHu JeiXiong LinjeiZhang BaojunHuang QiupingZhang QunLi MingzhenYang YaouWu QunWu QianShen QingpingGao KejianZhang ZhiminSun JunyanLin YouxinJin DepartmentofImmunology CollegeofBasicMedicalSciencesAnhuiMedicalUniversityHefei230032China. TheStatKeyLaboratoryofMolecularBiology InstituteofBiochemistryandCellBiologyShanghaiInstitutesforBiologicalSciencesChineseAcademyofScienceShanghaiChina. DepartmentofImmunology andSino-DanishJointLaboratoryofImmunologyWuhanUniversitySchoolofMedicineWuhan430071China. DepartmentofHematology TheAffiliatedUniversityHospitalAnhuiMedicalUniversityHefei230031China. DepartmentofHematology TheRenminandZongnanUniversityHospitalWuhanUniversityWuhan430071China. DepartmentofHematology TheProvincialHospitalofAnhuiHefei230020China.

We investigated CD19^+CD34^+ and CD19^+CD34 B cells from cord blood (CB) and typical patients with B cell lineage acute and chronic lymphocytic leukemia (B-ALL and B-CLL) in terms of expression and functions of CXCR5/CXCL13 and CCR7/***5 and CCR7 were selectively frequent expressed on B-ALL,B-CLL and CB CD19^+CD34^+ B cells,but not on CD19^+CD34 B *** of induction of impressive chemotactic responsiveness,CXCL13 and CCL19 together induced significant resistance to TNF-α-mediated apoptosis in B-ALL and B-CLL but not CB CD19^+CD34^+ B cells.B-ALL and B-CLL CD19^+CD34^+ B cells expressed elevated level of Paternally Expressed Gene 10 (PEG10),and CXCL13 and CCL19 together significantly up-regulated PEG10 expression in the *** found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulated PEG10 expression and function,subsequent stabilized caspase-3 and caspase-8 in B-ALL and B-CLL CD19^+CD34^+ B cells,and rescued the cells from TNF-α-mediated *** suggested that normal lymphocytes,especially naive B and T cells,utilized CXCR5/CXCL13 and CCR7/CCL19 for migration,homing,maturation,and cell homeostasis as well as secondary lymphoid tissues organogenesis. Meanwhile certain malignant cells took advantages of CXCR5/CXCL13 and CCR7/CCL19 for infiltration, resistance to apoptosis,and inappropriate *** & Molecular Immunology.2004;1(4):280-294.

关键词： leukemia B cells chemokine receptor apoptosis chemotaxis

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New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine

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Cellular & Molecular Immunology 2023年第7期20卷 739-776页

作者： Hanli Xu Shuye Lin Ziyun Zhou Duoduo Li Xiting Zhang Muhan Yu Ruoyi Zhao Yiheng Wang Junru Qian Xinyi Li Bohan Li Chuhan Wei Keqiang Chen Teizo Yoshimura Ji Ming Wang Jiaqiang Huang College of Life Sciences and Bioengineering School of Physical Science and EngineeringBeijing Jiaotong University3 ShangyuanCunHaidian District100044 BeijingP.R.China Cancer Research Center Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor Institute101149 BeijingChina Laboratory of Cancer Innovation Center for Cancer ResearchNational Cancer Institute at FrederickFrederickMD 21702USA.

Over the past thirty years,the importance of chemokines and their seven-transmembrane G protein-coupled receptors(GPCRs)has been increasingly *** interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes,including host homeostasis and responses to *** and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional *** and defects in the system contribute to the pathogenesis of a variety of diseases,including cancer,immune and inflammatory diseases,and metabolic and neurological disorders,which render the system a focus of studies aiming to discover therapies and important *** integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states,including,among others,coronavirus disease 2019(COVID-19).In this review,by reporting the latest advances in chemokine biology and results fromanalyses of a plethora of sequencing-based datasets,we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network,focusing on chemokine-mediated inflammation and *** of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.

关键词： chemokine chemokine receptor Migration Homeostasis Genetics Epigenetics

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Roles of chemokines in Thymopoiesis: Redundancy and Regulation

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Cellular & Molecular Immunology 2004年第4期1卷 266-273页

作者： WenxianFu WeifengChen DepartmentofImmunology SchoolofBasicMedicalSciencesPekingUniversityHealthScienceCenterBeijing100083China. DepartmentofImmunology SchoolofBasicMedicalSciencesPekingUniversityHealthScienceCenter38XueyuanRoadHaidianDistrictBeijing100083China.

Thymus is the primary lymphoid organ involved in the development of *** related events of thymocytes within thymus,especially the widely discussed directional migration of thymocytes,is regulated by chemokines via chemokine receptors mediated signaling *** types of chemokines and chemokine receptors,as components of the network-interaction within thymic microenvironment,are involved in the *** appears that these chemokines are functionally redundant and such phenomenon may be explained not only by the promiscuous,non-one-to-one matching between ligands-receptors within CXC or CC chemokine subfamily,but also by the various spatio-temporal expression patterns within different cell types and developmental *** redundancy and regulation of thymus expressed chemokines and chemokine receptors during thymocyte development are herein *** & Molecular Immunology. 2004;1(4):266-273.

关键词： chemokine chemokine receptor redundancy regulation thymopoiesis

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Up-Regulation of CCR5 and CXCR4 Expression on Human Monocytes by Interferon Gamma

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Tsinghua Science and Technology 2003年第4期8卷 440-444页

作者：陆韵刘祖强陈应华 Laboratory of Immunology Research Center for Medical Science Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China

chemokine receptors, mainly CCR5 and CXCR4, have been proved to be the important coreceptors in HIV 1 entry. HIV 1 disease progression is, in general, characterized by an initial predominance of CCR5 using macrophage tropic, non syncytium inducing (NSI) isolates, switching later to CXCR4 using T cell tropic, syncytium inducing (SI) isolates. How this shift occurs and how the shift can be controlled are still unclear. Since patients with rapid decline of T cell counts have constantly high levels of IFN γ in the sera and lymphoid nodes, we investigated the influence of this cytokine on the expression of the HIV 1 coreceptors CCR5 and CXCR4 on the cell surfaces of human monocytic cell line U937 and promonocyte NB4. IFN γ could intensively enhance the expression of both, while a low level of CCR5 expression was detected in two cell lines before stimulation. The results of semiquantitative RT PCR also confirm the up regulation. As the newly generated X4 strains have been demonstrated to be insensitive to chemokine in some reports, IFN γ may play an important role in selecting CXCR4 used strains.

关键词： HIV 1 IFN γ chemokine receptor CXCR4 CCR5

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The role of chemokines in acute and chronic hepatitis C infection

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Cellular & Molecular Immunology 2014年第1期11卷 25-40页

作者： Stephen Fahey Eugene Dempsey Aideen Long Institute of Molecular Medicine Trinity College Dublin Trinity Centre for Health Sciences St James's Hospital Dublin Ireland School of Biomolecular and Biomedical Science Conway Institute University College Dublin Dublin Ireland

Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus （HCV） succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.

关键词： chemokine chemokine receptor hepatic fibrosis hepatitis C virus immune evasion

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