Characterization of the human chemerin receptor--ChemR23/CMKLR1--as co-receptor for human and simian immunodeficiency virus infection, and identification of virus-binding receptor domains

Studies were conducted to elucidate co-receptor spectrum and function of the inflammatory receptor, CMKLR1/ChemR23, which was recently identified as the receptor for the cystatin-like chemoattractant, TIG2, also named chemerin. An infection model was applied based on stably transfected NP-2.CD4 host cells expressing various co-receptor constructs and exposed to panels of HIV-1, HIV-2 and SIV primary isolates. In a panel of 27 HIV-1 isolates tested, 12 isolates could use CMKLR1/ChemR23. As expected from a relatively high sequence homology with the extracellular domains of CCR3, HIV-1 isolates showing R3 tropism were particularly efficient in using CMKLR1/ChemR23. In addition, 5 out of 7 HIV-2 isolates and 13 out of 15 SIV (SMM-3 origin) used CMKLR1/ChemR23, in accordance with the previously documented ability of these isolates to use several co-receptors. In order to define important extracellular epitopes for the viral interaction, a hybrid receptor model was applied. This was based on the fact that the rat receptor, although structurally very similar to the human orthologue, was inefficient as viral co-receptor. When the rat receptor was "humanized" to include regions unique to the human receptor (N-terminus or second extracellular loop), exposure to HIV-1, HIV-2 and SIV isolates resulted in infection. The relative importance of the two critical receptor regions differed between HIV-1/HIV-2 on the one hand and SIV on the other. The results strongly support that the chemerin receptor, in the presence of CD4, functions as a "minor co-receptor" promoting infection by these classes of viruses.     

Chemerin activity in selected pathological states of human body – A systematic review

Recent studies have revealed that fatty tissue, so far considered an energy storage organ, is also the source of many substances called adipokines, including chemerin which plays many important functions in the body. Chemerin stimulates adipocytes maturation and differentiation, as well as acts as a chemoattractant, which stimulates innate and acquired immunity. This adipokine participates in the early stages of acute inflammation as well as its suppression by reacting with the CMKLR1 receptor. In various diseases associated with inflammatory processes, the level of chemerin in the serum increases. It is also considered a marker for benign and malignant tumors. Explanation of the pathomechanisms involving this adipokine is of a high importance and may contribute to the development of new possibilities in the treatment of many diseases. The article presents the latest information on the role of chemerin in various pathological states, particularly in psoriasis.     

非ST段抬高心肌梗死和不稳定心绞痛患者血浆脂肪激素Chemerin水平及其影响因素研究

目的探讨非ST段抬高性心肌梗死和不稳定心绞痛(NSTEMI/UA)患者血浆脂肪激素Chemerin水平及其影响因素。方法收集因胸痛住院并行冠状动脉造影的患者121例,根据患者的临床表现和冠状动脉造影结果分组:对照组44例、稳定冠心病组40例和NSTEMI/UA组37例。空腹抽血,测定血浆脂肪激素Chemerin水平及其他生化指标,如空腹血糖、血脂、肌酐、超敏C反应蛋白(hs-CRP)、白细胞、血浆纤维蛋白原等水平。结果与对照组和稳定性冠心病组比较,NSTEMI/UA组血浆脂肪激素Chemerin水平升高〔(229.45±25.47)ng/ml、(203.82±9.89)ng/ml和(214.53±12.24 ng/mL)ng/ml,P<0.05〕。Pearson相关分析表明血浆脂肪激素Chemerin水平与入院时心率、白细胞总数、中性粒细胞、hs-CRP、纤维蛋白原、空腹血糖、肌酐呈正相关关系(r值分别为0.605、0.583、0.610、0.608、0.553、0.558和0.674,P<0.001)。结论 NSTEMI/UA患者血浆脂肪激素Chemerin水平明显升高,并与入院时心率、白细胞、中性粒细胞、hs-CRP、纤维蛋白原、空腹血糖和肌酐水平密切相关,提示Chemerin可能与不稳定斑块和继发血栓形成有关。     

大鼠肾周脂肪组织趋化因子样受体1过表达对非酒精性脂肪性肝炎的影响*

目的 探讨慢病毒介导的趋化因子样受体1（CMKLR1) 在大鼠肾周脂肪组织中过表达对非酒精性脂肪性肝炎的影响。方法 将42只雄性SD大鼠随机分为对照组、模型组、转染组各12只和空转染组6只。给予对照组普通饮食喂养,给予其余组高脂饮食喂养。在造模开始时给予各组经尾静脉注射溶媒和真病毒或空病毒。在实验第8 w和12 w,分批处死大鼠,取肝组织行苏木精-伊红染色,观察组织病理学变化;采用酶联免疫吸附法测定血清凯莫瑞和脂联素水平;分别采用RT-PCR法和Western blot法测定肾周脂肪组织CMKLR1和脂联素mRNA和它们的蛋白表达。结果 模型组大鼠肝组织炎症程度明显于对照组和转染组;在实验8 w和12 w,模型组血清凯莫瑞水平分别为（4.65±0.48） mmol/L和 (4.47±0.37）mmol/L,与对照组水平无明显差异[（4.38±0.43）mmol/L和（4.16±0.27）mmol/L],但均显著低于转染组水平[（7.66±0.53）mmol/L和（6.74±0.59）mmol/L,P<0.05];在8 w时,模型组脂肪组织CMKLR1 mRNA及其蛋白相对量分别为（0.235±0.008）和（0.206±0.005）,与对照组水平无显著差异[（0.226±0.008）和（0.21±0.117）],但显著低于转染组水平[（0.579±0.016）和（0.504±0.121）,P＜0.05];第12 w时,脂肪组织CMKLR1 mRNA及其蛋白表达水平与第8 w时结果相似;在8 w时,模型组大鼠血清脂联素水平、脂肪组织脂联素 mRNA及其蛋白表达水平分别为[【（31.82±1.51）mmol/L、（0.126±0.005）和（0.14±0.008）],显著低于对照组[（37.92±4.09）mmol/L、（0.262±0.007）和（0.35±0.016）,P<0.05]和转染组水平[（36.50±2.43）mmol/L、（0.193±0.058）和（0.232±0.012）,P<0.05];在12 w时,所测血清脂联素水平、脂肪组织脂联素 mRNA水平及其蛋白表达水平与第8 w时结果相似。结论 慢病毒介导的大鼠脂肪组织内过表达CMKLR1可显著改善大鼠非酒精性脂肪性肝炎时肝组织病理学损害。     

Chemerin与动脉粥样硬化的关系

新发现的脂肪细胞因子chemerin不仅是传统意义上的趋化蛋白,还通过多种途径参与动脉粥样硬化的发展.其可能机制是参与胰岛素抵抗,糖、脂代谢异常及代谢综合征的发生,进而促进动脉粥样硬化的发展;直接影响血管内皮细胞的炎性反应状态,促进单核巨噬细胞黏附、迁移以及泡沫细胞的形成;促进新生血管形成,使斑块不稳定性增加,参与斑块破裂、血栓形成.深入研究chemerin与动脉粥样硬化的关系将为动脉粥样硬化的防治提供新靶点.     

二甲双胍对胰岛素抵抗大鼠内脏脂肪组织chemerin表达的影响

将雄性4周龄SD大鼠分为正常饲料组和高脂饲料组,喂养10周后分别以二甲双胍治疗(200mg/kg)6周.以正常血糖-高胰岛素钳夹试验评估胰岛素敏感性,留取肾周脂肪组织,采用实时定量PCR及Western印迹法检测脂肪组织中chemerin mRNA和蛋白的表达水平.结果显示,高脂饲料诱导的胰岛素抵抗、大鼠肾周脂肪组织chemerin mRNA和蛋白水平高于正常饲料喂养大鼠(均P＜0.05),二甲双胍治疗6周后明显降低(均P＜0.01).脂肪组织中chemerin mRNA、蛋白表达水平均与附睾脂肪质量指数显著相关(均P＜0.05).     

Adiponectin upregulates hepatocyte CMKLR1 which is reduced in human fatty liver

Chemokine-like receptor 1 (CMKLR1) ligands chemerin and resolvin E1 are suggested to have a role in non-alcoholic fatty liver disease (NAFLD). Here, expression of CMKLR1 in liver cells and NAFLD was studied. CMKLR1 was detected in primary human hepatocytes (PHH), Kupffer cells, bile-duct cells and hepatic stellate cells. In human and rodent fatty liver and in fibrotic liver of mice fed a methionine-choline deficient diet CMKLR1 was reduced. Hepatocytes are the major cells in the liver and effects of adipokines, cytokines and lipids on CMKLR1 in PHH were analyzed. Increased cellular triglyceride or cholesterol content, lipopolysaccharide, IL-6, TNF and leptin did not influence CMKLR1 levels in PHH whereas profibrotic TGFβ tended to reduce CMKLR1. Adiponectin strongly upregulated CMKLR1 mRNA and protein in PHH and hepatic CMKLR1 when injected into wild type mice. Further, CMKLR1 was suppressed in the liver of adiponectin deficient mice. These data indicate that low CMKLR1 in NAFLD may partly result from reduced adiponectin activity.     

银屑病患者中趋化素与皮损、肥胖、糖脂代谢及炎症因子的相关性

目的分析趋化素（Chemerin）水平与银屑病（PS）患者皮损严重程度、肥胖、糖脂的代谢紊乱、炎症因子的相关性。 方法选择2019年1月至2020年1月于广西医科大学第一附属医院收治的150例PS患者,根据PS患者是否并发代谢综合征（MS）分为单纯PS组及PSMS组,同期选择于本院查体中心查体的健康人群40例为对照组。测量并记录各组受检者的身高、体重及腰围（WC）,计算身体质量指数（BMI）。采用PS面积与严重程度指数（PASI）量表评估2组患者的皮损严重程度。采集所有受检者空腹静脉血5 ml,采用全自动生化分析仪检测血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、空腹血糖（FPG）,采用放射免疫分析法检测血清空腹胰岛素（Fins）、超敏C反应蛋白（hs-CRP）、白介素6（IL-6）,计算胰岛素抵抗指数（HOMA-IR）,采用酶联免疫吸附法检测血清趋化素水平。 结果单纯PS组及PSMS组患者血清趋化素水平明显高于对照组,PSMS组患者血清趋化素水平明显高于单纯PS组（P＜0.01）。单纯PS组及PSMS组患者血清hs-CRP、IL-6水平明显高于对照组,PSMS组患者血清hs-CRP、IL-6水平明显高于单纯PS组（P＜0.01）。单纯PS组及PSMS组患者BMI、WC、TG、TC、LDL-C、Fins及HOMA-IR水平明显高于对照组,PSMS组患者BMI、WC、TG、TC、LDL-C、Fins及HOMA-IR水平明显高于单纯PS组,HDL-C水平明显低于对照组及单纯PS组（P＜0.01）。单纯PS组患者Fins及HOMA-IR水平明显高于对照组,PSMS组患者PASI水平明显高于单纯PS组（P＜0.01）。Pearson线性相关分析得知,趋化素与PASI、BMI、WC、TG、LDL-C、hs-CRP、IL-6均呈明显正相关（P均＜0.05或＜0.01）。进一步以血清趋化素为因变量,将与因变量具有线性关系的PASI、BMI、WC、TG、LDL-C、hs-CRP、IL-6为自变量进行多元逐步回归分析得知,WC、TG、hs-CRP、IL-6对趋化素存在影响（P均＜0.05或＜0.01）。 结论趋化素参与PS的发生及发展过程,其水平的变化与PS患者的病情严重程度、肥胖、糖脂代谢紊乱及炎症反应存在密切联系,为评估PS病情发展及有效治疗PS提供新的思路。     

缺血性脑血管疾病患者Chemerin因子与高同型半胱氨酸血症的关系

目的探讨缺血性脑血管病(ICVD)患者血清Chemerin因子水平与高同型半胱氨酸血症(HHcy)的相关性。方法行全脑数字减影血管造影术(DSA)检查的ICVD患者60例,以动脉狭窄率50%为分组依据:狭窄组30例(A组),患者颅内、外脑大动脉≥1支血管狭窄率≥50%;轻度狭窄组30例(B组),患者动脉狭窄50%。另选取30例健康体检者对照组(C组)。检测血清Chemerin及同型半胱氨酸(Hcy)浓度,同时测定各组血压及生化指标。结果 A组Chemerin、Hcy、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)水平及收缩压(SBP)均显著高于B组(P0.05),且A、B组上述指标均显著高于C组(P0.05)。3组HHcy发生率有显著差异(P0.05)。血清Chemerin与动脉狭窄率、HHcy发生率呈显著正相关(P0.05)。结论血清Chemerin及Hcy水平与脑大动脉狭窄程度相关。血清Chemerin水平与HHcy发生率呈正相关,可作为ICVD发生发展的一个预测指标。     

血清趋化素、网膜素-1水平与缺血性脑血管病颈动脉狭窄的相关性

目的 探究血清趋化素、网膜素-1水平与缺血性脑血管病（ICVD）病人颈动脉狭窄的相关性。方法 选取2017年2月至2020年1月在沧州市中心医院诊治ICVD病人60例为研究对象,并选择同期30例健康体检者为对照组。收集所有病人的一般临床资料。ICVD病人均接受数字减影血管造影（DSA）并计算动脉狭窄率,并将病人分为轻度狭窄组和中重度狭窄组,采用双抗体夹心免疫吸附法检测病人血清趋化素、网膜素-1水平。检测三组病人的实验室指标,并采用Pearson相关性分析趋化素、网膜素-1水平与实验室指标的关系。ROC曲线分析趋化素、网膜素-1对病人发生中重度狭窄的评估价值。结果 与对照组相比,轻度狭窄组和中重度狭窄组病人血清趋化素水平依次升高,而网膜素-1水平依次下降,均差异有统计学意义（P<0.05）。实验室指标检测结果显示,与对照组相比,轻度狭窄组和中重度狭窄组病人收缩压（SBP）、三酰甘油（TG）、空腹血糖（FPG）和C反应蛋白（CRP）水平均显著升高（P<0.05）,而高密度脂蛋白胆固醇（HDL-C）水平显著降低（P<0.05）。与轻度狭窄组病人相比,中重度狭窄组病人SBP、...