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Expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model, selectively induced by IL-4 and IL-10, regulates the embryo resorption rate

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Chinese Medical Journal 2009年第16期122卷 1917-1921页

作者： JIANG Pei-juan ZHAO Ai-min BAO Shi-min XIAO Shi-jin XIONG Miao Department of Obstetrics and Gynecology Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200127 China Laboratory Animal Center of Shanghai Chinese Academy of Science Shanghai 201615 China Department of Obstetrics and Gynecology Shanghai Pudong New Area Gongli Hospital Shanghai 200135 China

Background chemokines and their receptors have been a research focus in transplantation immunology. chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy. Methods The mouse model of spontaneous abortion （CBA/J×DBA/2） and the normal pregnant mouse model （CBA/J×BALB/c） were used. CBA/J×DBA/2 mice were injected with IL-4 （CBA/J×DBA/2-IL-4）, IL-4 and IL-10 （CBA/J×DBA/2-IL-4＋IL-10）, or normal saline （CBA/J×DBA/2-NS） as a control. The expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined. Results The embryo resorption rate in the CBA/J×DBA/2 group without any treatment was significantly higher than that in the CBA/J×BALB/c group （17.9% vs 3.7%, P 〈0.01）. The embryo resorption rate in the CBA/J×DBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4^＋ T cells in the CBA/J×DBA/2 group without any treatment was significantly lower than that in the CBA/J×BALB/c group （0.3738±0.3575 vs 1.2190±0.2772, P 〈0.01）; both CCR5 （3.0900±1.5603 vs 1.2390±0.6361, P〈0.01） and CXCR3 （2.4715±0.9074 vs 0.9200±0.5585, P 〈0.01） expressions on CD4^＋ T cells of the CBA/J×DBA/2 group without any treatment were significantly higher than those of the CBA/J×BALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/J×DBA/2 group treated with IL-4 （CCR3： 2.0360±0.6944, CXCR3： 1.3510±0.5263, P〈0.01） or IL-4 and IL-10 （CCR3： 1.8160±1.0947, CXCR3：1.0940±0.7168, P〈0.01）. Because of the CCR5, IL-4 and IL-10 （1.9400±0.8504 vs 3.0900±1.5603, P 〈0.0

关键词： chemokine receptors CD4-positive T-lymphocytes abortion, spontaneous interleukin-4 interleukin-10

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mRNA Expression of chemokine receptors on Peripheral Blood Mononuclear Cells and Correlation with Clinical Features in Systemic Lupus Erythematosus Patients

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Chinese Medical Sciences Journal 2010年第3期25卷 162-168页

作者： Yu-mei Li Zhi-qiang Chen Xu Yao Ai-zhen Yang An-sheng Li Dong-ming Liu Juan-qin Gong Department of Dermatology Hospital for Skin Diseases Chinese Academy of Medical Sciences ＆ Peking Union Medical College Nanjing 210042 China Central Lab of People＇s Liberation Army Cancer Center the 81st Military Hospital Nanjing 210002 China Department of Medical Imaging and Radiology the Affiliated Hospital of Jiangsu University Zhenjiang 212001 China

Objective To investigate the expressions of chemokine receptors and interleukin （IL） receptors on the peripheral blood mononuclear cells （PBMCs） from systemic lupus erythematosus （SLE） patients and their correlations with clinical features as well as SLE disease activity index （SLEDAI）. Methods The mRNA expressions of chemokine receptors and IL receptors on PBMCs of 93 SLE patients and 30 healthy controls were detected by reverse transcription-polymerase chain reaction, including CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCR5, CX3CR1, XCR1, IL-4R, and IL-10R. The clinical features of SLE patients were recorded. The correlations of chemokine receptors and IL receptors mRNA expressions with clinical features as well as SLEDAI were assayed using linear regression analysis. Results The level of CCR5 mRNA in SLE patients （including active and inactive SLE） was signifi- cantly higher than that in healthy controls （P〈0.05）, and there was no significant difference between active and inactive patients in this respect （P〉0.05）. CX3CR1 mRNA expression significantly increased from healthy control to inactive SLE to active SLE in sequence. The others （except for CCR8, CXCR3, and IL-1 OR） in active SLE patients weresignificantly higher than those in both inactive SLE patients and healthy controls （all P〈0.05）. There were positive correlations between SLEDAI and CCR2 （r=0.424, t=4.313, P〈0.001）, CCR3 （r=0.518, t=5.410, P〈0.001）, CCR4 （r=0.376, t=3.851, P〈0.001）, CCR6 （r=0.457, t=4.513,P〈0.001）, CXCR5 （r=0.455, t=4.629, P〈0.001）, CX3CR1 （r=0.44-5, t=4.523, P〈0.001）, as well as XCRI （r=0.540, t=5.445, P〈0.001）. And CCR5 mRNA expression level was positively correlated with IL-4R mRNA （r=0.313, t=2.353, P〈0.05）. The patients with myositis and cutaneous vasculitis simultaneously showed lower levels of CCR5 and CX3CRI, and CCR5 expression was negatively correlated with the scores of SLEDAI in SLE cases accompanied by photosensitivity （r=0.426, t=- 2.155, P〈0.05）. Conclusion Increas

关键词： systemic lupus erythematosus chemokine receptors peripheral bloodmononuclear cell

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chemokine receptors CCR1, CCR3, CCR7 and chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for Acute Rejection Diagnosis of Kidney Transplants

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Open Journal of Nephrology 2023年第2期13卷 126-149页

作者： Paula Xavier Dias-Pinto José Gerardo G. Oliveira Portuguese Blood and Transplantation Institute Porto Portugal Faculty of Medicine University of Porto Porto Portugal CINTESIS FMUP Porto Portugal

Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.

关键词： Kidney Transplants Aspiration Biopsies Acute Rejection chemokines chemokine receptors

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The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis

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Cellular & Molecular Immunology 2023年第7期20卷 714-738页

作者： Teizo Yoshimura Chunning Li Yuze Wang Akihiro Matsukawa Department of Pathology and Experimental Medicine Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama University2-5-1 ShikataKita-kuOkayama 700-8558Japan.

Breast cancer is the most prevalent cancer worldwide,and metastasis is the leading cause of death in cancer *** monocyte chemoattractant protein-1(MCP-1/CCL2)was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human ***-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages(TAMs),and it became a candidate target of clinical intervention;however,the role of TAMs in cancer development was still controversial at the time of the discovery of *** in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues,including breast *** correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were *** contribution of MCP-1 to the growth of primary tumors and metastasis to the lung,bone,and brain was examined in mouse breast cancer *** results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not *** mechanisms of MCP-1 production in the breast cancer microenvironment have also been *** the present manuscript,we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis.

关键词： Breast cancer chemokines chemokine receptors metastasis macrophages

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chemokine expression in hepatocellular carcinoma versus colorectal liver metastases

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World Journal of Gastroenterology 2006年第41期12卷 6627-6633页

作者： Claudia Rubie Vilma Oliveira Frick Mathias Wagner Christina Weber Bianca Kruse Katja Kempf Jochen Knig Bettina Rau Martin Schilling Department of General- Visceral-Vascular-and Paediatric SurgeryUniversity of the SaarlandHomburg/Saar 66421Germany Institute of Pathology University of the SaarlandHomburg/Saar 66421Germany Institute of Medical Biometrics Epidemiologyand Medical InformaticsUniversity of the SaarlandHomburg/ Saar 66421Germany

AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （HCC） versus colorectal liver metastases （CRLM） and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS： chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS： Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION： Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.

关键词： chemokines chemokine receptors Gene expression Hepatocellular carcinoma Colorectal liver metastases

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Ampelopsin, a Small Molecule Inhibitor of HIV-1 Infection Targeting HIV Entry

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Biomedical and Environmental Sciences 2004年第2期17卷 153-164页

作者： DE-YULIU JIAN-TAOYE WEN-HUIYANG JINYAN CHANG-HONGZENG SAZENG DepartmentofChemistry ZhongshanMedicalCollegeSunYat-senUniversityGuangzhou510089GuangdongChina／／ GuangdongProvincialCenterforDiseasePreventionandControl Guangzhou510300GuangdongChina

Objective To investigate the anti-HIV effects of ampelopsin and its interaction with HIV-1 coreceptor CXCR4. Methods Through anti-virus experiments in vitro, the inhibitory effect of ampelopsin on HTV-1 infection was verified. Chemotaxis assay was performed to show the ability to induce PBMCs migration by ampelopsin, RANTES and SDF-la. Fluorescence labelling monoclonal antibody was utilized to observe the interaction of ampelopsin and CXCR4. Mice immunosuppressant model was also established to detail the role ampelopsin played in regulating cellular immunological functions. Results Ampelopsin could protect sensitive cells against HTV-1 infection and dramatically reduce HIV-1 antigen P24 expression. HTV-1SF33 attaching to MT-4 cells was interfered by ampelopsin, and the EC50 was 0.175 mg/mL for cellular protection and 0.024 mg/mL for P24 inhibition. At co-cultivating phase, EC50 was 0.229 mg/mL and 0.197 mg/mL respectively. Furthermore, the EC50 was 0.179 mg/mL and 0.348 mg/mL in acute infection. Human PBMCs migration was induced after being challenged with ampelopsin or chemokines, and synergistic action was observed during co-treatment. Ampelopsin alone resulted in maximal chemotaxis at 1 mg/mL. HIV-1 co-receptor CXCR4 on the surface of PBMCs was decreased by internalization, which indicated the effect of ampelopsin on CXCR4. About 70% CXCR4 was reduced by ampelopsin at 1 mg/mL. Ampelopsin also augmented cellular immunological functions in immunosuppressive mice. Conclusion Ampelopsin displays a strong inhibitive role during HIV-1 absorption, incubation and acute infection. These results are coincident with its immune enhancement.

关键词： Ampelopsin HTV-1 chemokine receptors Cellular immunity

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Molecular targets in the treatment of alcoholic hepatitis

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World Journal of Gastroenterology 2012年第39期18卷 5504-5513页

作者： Ashwin D Dhanda Richard WL Lee Peter L Collins C Anne McCune Department of Liver Medicine University Hospitals Bristol NHS Foundation TrustBS2 8HW BristolUnited Kingdom Department of Cellular and Molecular Medicine School of Clinical SciencesUniversity of BristolBS9 1TD BristolUnited Kingdom

Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease.

关键词： Alcoholic hepatitis Tumour necrosis factor-m Pentoxifylline Interleukins chemokine receptors

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Spatial Genetic Structure of Two HIV-I-resistant Polymorphisms (CCR2-64 Ⅰ and SDF1-3’A) Alleles in Population of Shandong Province, China

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Biomedical and Environmental Sciences 2005年第4期18卷 241-253页

作者： FU-ZHONG XUE JIE-ZHEN WANG DAO-XIN MA GUO-RONG LI PING HU Department of Epidemiology and Biostatistics School of Public Health Shandong University Jinan 250012 ShandongChina Qilu Hospital Shandong University Jinan 250012 Shandong China Center for Disease Control and Prevention of Shandong Province Jinan 250012 Shandong China

To explore the spatial genetic structure of two HIV-Ⅰ-resistant polymorphisms （CCR2-64 Ⅰ and SDF1-3＇A） alleles in the population of Shandong Province, China. Methods Using the techniques of spatial stratified sampling and spatial statistics, the spatial genetic structure of the locus （CCR2-64 Ⅰ and SDF1-3＇A）, which was shown to be important co-receptor for HIV infection, was quantified from the populations of 36 sampled counties of Shandong Province, and a total of 3147 and 3172 samples were taken for testing CCR2-64Ⅰ and SDF1-3＇A respectively from individuals without known history of HIV-Ⅰ infection and AIDS symptoms. Results There were significantly spatial genetic structures of the two alleles at different spatial distance classes on the scale of populations, but on the scale of individuals, no spatial structure was found in either the whole area of Shandong Province or the area of each sampled county. Although the change of frequencies of the two alleles with geographic locations in Shandong Province both showed gradual increase trends, their changing directions were inverse. The frequency of CCR2-64Ⅰallele gradually increased from the southwest to the northeast, while the frequency of SDF1-3＇A allele gradually increased from the northeast to the southwest. However the RH to AIDS of combined types of their different genotypes did not represent obvious geographic diversity on the whole area of the Province. Conclusion The frequency of allele usually has some spatial genetic structures or spatial autocorrelation with different spatial distance classes, but the genotypes of individuals have random distribution in the same geographic area. Evaluating spatial distribution of the genetic susceptibility of HIV （AIDS） to CCR2-64Ⅰand SDF1-3＇A alleles, should focus on the frequencies of combined genotypes of CCR2 and SDFI based on the two-locus genotypes of each individual rather than the frequencies of CCR2-641 and SDF1-3＇A alleles.

关键词： Spatial genetic structure chemokine receptors HIV-Ⅰ Resistant polymorphism Relative hazard

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Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

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World Journal of Gastroenterology 2008年第47期14卷 7149-7159页

作者： Juan R Larrubia Selma Benito-Martínez Miryam Calvino Eduardo Sanz-de-Villalobos Trinidad Parra-Cid Department of Gastroenterology Guadalajara University HospitalUniversity of AlcaláDonante de Sangre st.19002 GuadalajaraSpain Guadalajara University Hospital University of AlcaláDonante de Sangre st.19002 GuadalajaraSpain

chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected *** milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) *** chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine *** and peripheral blood levels of these chemokines are increased during chronic hepatitis *** interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the *** the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic *** modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell *** chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response *** regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.

关键词： chemokines chemokine receptors Hepatitis C virus Viral hepatitis pathogenesis Persistentinfection Viral escape mechanism

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