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趋化因子及其受体在病毒性疾病中的作用
趋化因子( chemokine)是一类三维结构上相似,唯一的一类通过G蛋白偶联受体超家族起作用的细胞因子.趋化因子及其受体主要介导了细胞的定向移动,参与免疫细胞和器官的发育、免疫应答过程、病原体感染与清除、肿瘤形成和转移,此外近年来还报道趋化因子可扮演神经调质和细胞凋亡促进因子的角色,发挥广泛的生理和病理作用.本文将从趋化因子及其受体的结构、分类和免疫反应中的功能展开综述,着重阐述了在病毒感染引发的病理损伤过程中趋化因子及其受体的功能,为病理诊断和相关病毒性疾病的干预提供了线索和思路.
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CCR7在恶性肿瘤细胞侵袭及淋巴定向转移中的作用
CCR7 属于CC 类趋化因子受体,曾用名EBI-1、BLR-2 和CMKBR2,含378 个氨基酸残基,基因定位于17q12 ~q21.2.与其结合的CC 类趋化因子配体为CCL21(也称为次级淋巴组织趋化因子,secondary lymphoid-tissue chemokine,SCL)和CCL19 (也称为EBI1 配体趋化因子,EBI1-ligand chemokine,ELC),均特异性高表达于淋巴结、扁桃体、非淋巴组织的内皮淋巴导管、脾T 细胞富集区及淋巴内皮中.
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急性冠状动脉综合征患者血浆人CXC趋化因子配体16检测及其临床意义
ACS包括UAP、NSTEMI和STEMI,是严重威胁人类生命的重大疾病之一,其病变为动脉粥样硬化形成基础上的粥样斑块不稳定、破裂和继发血栓形成.人CXC趋化因子配体16(CXC chemokine ligand16,CXCL16)是属于CXC趋化因子亚家族的重要成员,它以可溶性或跨膜表达2种形式存在,具有趋化因子、清道夫受体及黏附分子等3种分子的功能,在动脉粥样硬化的发生发展中起重要作用[1-2].可溶性CXCL16进入血液循环后其浓度稳定且可达1 μg/L以上,但血清CXCL16能否成为一种冠心病的无创诊断标志目前尚存在争议[1].Sheikine等[3]发现冠心病,包括ACS及稳定型心绞痛患者血浆CXCL16水平均低于健康对照组[3].但随后的研究却发现冠心病患者的血浆CXCL16水平显著高于健康对照组,尤其是ACS患者[4-5].本研究采用ELISA法定量检测ACS患者血浆CXCL16水平,探讨血浆CXCL16水平与ACS之间的关系.
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趋化因子CX3CL1及其受体在肝脏炎症和纤维化中的作用
趋化因子(chemokine)是使细胞发生趋化运动的小分子细胞因子,其对不同靶细胞具有一定趋化效应.近年来研究表明趋化因子在急、慢性肝病起重要作用,其通过浓度梯度趋化免疫细胞(如T细胞、NK细胞)渗入受损的肝脏.不仅如此,随着炎症及纤维化反应,趋化因子还可直接影响肝内细胞,如肝星状细胞(hepatic stellate cell,HSC)、肝细胞.
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趋化因子及趋化因子受体在骨肉瘤中的研究进展
骨肉瘤,又称成骨肉瘤,是常见的恶性成骨性肿瘤之一,占恶性骨肿瘤总数的20%~45%,多数起源于骨间叶细胞。发病年龄多在15~25岁之间,男性多于女性。好发部位为长骨干骺端,其中以股骨远端和胫骨近端较多见,其次是肱骨和腓骨近端,随血液运行转移率高且早,发展迅速。骨肉瘤侵袭性强,约20%的患者发生转移,肺转移为常见[1]。随着新辅助化疗、保肢手术等的开展,骨肉瘤患者5年生存率提高到60%~70%[2]。但由于化疗耐药性、转移率高等问题的存在,患者仍面临着复发及肺转移的困扰。基因治疗、免疫治疗和分子靶向治疗等生物治疗技术的发展也为骨肉瘤的治疗开辟了新的道路,为骨肉瘤患者带来新的希望[3]。
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HIV entry inhibitors: progress in development and application
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MCP-1及 HIF-1与肿瘤血管生成关系的研究进展
一、 MCP-1与肿瘤血管生成的关系1.MCP-1的生物学特性:(1)趋化因子及受体:趋化因子(chemokine)是能使细胞向高浓度刺激物方向做定向运动的小分子细胞因子,为一类结构、功能相似,相对分子质量8~10kDa小相对分子质量蛋白质.对多种细胞(如白细胞、肿瘤细胞)具有趋化作用(使其作定向运动).可由多种细胞产生,如淋巴细胞、NK细胞、中性粒细胞、单核-吞噬细胞、成纤维细胞、内皮细胞、平滑肌细胞乃至上皮细胞和肿瘤细胞等.自1987 年发现第1个趋化因子IL-8 至今已发现并克隆出趋化因子达50 余种[1] .
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Objective To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation,normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC-CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocytederived dendritic cells (MoDCs).The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was alsso studied.Methods In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratoly ability was assessed by a micromultiwell chemotaxis chamber assay.Results IL-8, MCP-1, RANTES and their corresponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable efter 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present.Conclusion Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses.
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SDF-1/CXCR4与肾脏疾病关系的研究进展
基质细胞衍生因子-1(stromal cell derived factor-1,SDF-1)是新近发现的一种细胞因子,属CXC(Cys-X-Cys)类趋化蛋白,系统命名CXCL12(CXC chemokine ligand12),是已知唯一能与受体CXCR4结合并激活的天然趋化因子.
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趋化因子XCL1的免疫调节作用与相关疾病的研究
趋化因子(chemokine)是一类对不同靶细胞具有趋化效应的的细胞因子家族,已发现50多个成员.该家族成员依据其分子氨基端半胱氨酸的数目及其间隔,可分为CC、CXC、C、CX3C四个亚家族.趋化因子能诱导白细胞及其他类型的体细胞定向迁移和活化,而且在免疫细胞和器官的发育、免疫应答、炎症反应、病原体感染、创伤修复及肿瘤形成和转移等方面发挥广泛的生理和病理作用[1].
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SDF-1/CXCR7生物学轴与肿瘤的研究进展
历来认为趋化因子受体4(chemokine receptor 4,CXCR4)是趋化因子SDF-1的唯一受体,SDF-1/CXCR4生物学轴在肿瘤的发生发展过程中起重要作用,近研究发现SDF-1存在另一个受体CXCR7,并且SPF-1/CXCR7生物学轴同样对肿瘤的发生发展起着重要的作用.本文就SPF-1/CXCR7生物学轴在肿瘤中的增殖、侵袭、转移以及肿瘤治疗等方面的研究作一综述.
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Cellular chemokine CCL18increases matrix metalloproteinases expression and promotes ovarian cancer cell invasion and metastasis in vivo
Objective:To study the effect of cell chemokine (C-C motif) ligand 18 (CCL18) on ovarian cancer proliferation and metastasis.Methods:This study first analyzed the effects of overexpression of CCL18 on the growth in a subcutaneous ovarian cancer xenografts mouse model.Real-time quantitative PCR was used to detect the expression of matrix metalloproteinases (MMPs) in xenografts tissues.Then,an ovarian cancer orthotropic xenografts model was used to access the effect of CCL18 on ovarian cancer metastasis.Results:Over expressing CCL18 in SKOV3 cells did not significantly promote the tumor growth of subcutaneous xenografts.But the mRNA levels of MMP1,MMP7,MMP11 and MMP15 were significantly inncreased (P < 0.05).The mRNA level of MMP12 was not changed (P >0.05).In orthotopic xenografts ovarian cancer mouse model,metastasis appeared in more organs in CCL 18 overexpressed SKOV3 cells than GFP/SKOV3 cells.Conclusion:CCL18 increased the expresston of MMPs in ovarian cancer cells and promoted metastasis of ovarian cancer cells in vivo.
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Targeting CC Chemokine Ligand 2 (CCL2) for Cancer Skeletal Metastasis
Prostate, breast, and lung cancer preferentially metastasize to bone result-ing in bone lesions and thus high mortality.
关键词: chemokine lung cancer High