CD40／CD40L介导信号的免疫调节作用

Ｂ细胞的ＣＤ４０分子与活化Ｔ细胞的ＣＤ４０配体（ＣＤ４０Ｌ）结合可调节Ｂ细胞生长分化、克隆转换、Ｉｇ分泌、阻断Ｂ细胞凋亡和导Ｆａｓ表面分隔表达等,直接参与调节体液免疫。ＣＤ４０与ＣＤ４０Ｌ结合也影响细胞免疫功能,诱导Ｔｈ１和Ｔｈ２细胞因子产生《ＣＤ４０和ＣＤ４０Ｌ连接ＴＲＡＦ蛋白多聚化,从而调节基因的转录。ＣＤ４０介导的信号传导过程与蛋白酷氨酸酶、蛋白酪氨酸磷酸化有等有关。     

CD40/CD40L信号系统与子痫前期的关系

子痫前期是病理产科中常见的疾病,是导致孕产妇和围生儿死亡的主要原因,其具体病因目前尚未完全阐明,大多数学者认为主要与氧化应激导致的血管内皮细胞损伤,胎盘浅着床,免疫平衡的破坏等因素有关,其中内皮细胞损伤导致的内皮细胞生理功能失衡是其病因学研究的热点.CD40/CD40L是一对互补的肿瘤坏死因子和肿瘤坏子因子受体超家族跨膜糖蛋白,相互作用可以促进内皮细胞、平滑肌细胞表达和释放细胞因子、组织因子、金属蛋白酶、粘附分子,这些物质间接或直接的参与了炎症反应和免疫调节,导致内皮细胞损伤.因此,CD40/CD40L相互作用在炎症反应和免疫失调中亦起着关键作用,可能是子痫前期的病因之一,以CD40/CD40L为靶点为子痫前期的诊断和治疗提供了新的思路和方向.本文拟对CD40/CD40L信号系统与子痫前期的关系做一综述.     

CD40-CD40L与斑块的不稳定性

随着对动脉粥样硬化性疾病研究的深入,人们发现众多的心脑血管疾病是由于粥样斑块不稳定所引起。近来研究表明CD40-CD40L不仅在免疫炎症反应中起着重要作用,同时影响斑块的稳定性。     

GMPS,PR,CD40和p21对卵巢癌预后的预测价值(Prognostic values of GMPS,PR CD40,and p21 in ovarian cancer全译)

目的通过一个卵巢癌自发恶性转化模型来识别卵巢癌患者的预后标志物。方法小鼠卵巢表面上皮细胞(MOSECs)在体外培养可以发生自发恶性转化。使用Illumina HiSeq 2000新一代测序平台和生物信息学分析检测在此模型转化过程中的基因表达和信号传导的改变。使用基因表达互作谱分析(http://gepia.cancer-pku.cn/)识别4个差异表达的核心基因,随后使用TCGA数据库与Kaplan-Meier Plotter在线数据库(www.kmplot.com)研究这些核心基因与卵巢癌患者生存期之间的关系。结果数据显示在MOSECs自发恶性转化的初期与晚期差异表达的基因共计263个,其中包括182个上调与81个下调基因。生物信息学数据揭示有4个基因(GMPS、PR、CD40、p21)在卵巢癌发生过程中扮演者重要的角色。此外,使用TCGA数据验证了这4个基因的差异表达及其与卵巢癌患者的预后相关。结论本研究使用卵巢癌进展模型分析差异表达的基因,并鉴定出四种(即GMPS、PR、CD40和p21)基因可以作为卵巢癌患者的预后标志物。未来需要前瞻临床研究来进一步验证这四种基因的特征及其临床实用性。     

CD40-CD40L功能与疾病的研究进展

CD40与CD40L的相互作用不仅在细胞免疫和 体液免疫中起作用,而且在疾病的发病机制和临床治疗中起重要作用。     

Bioactivity of nitrolinoleate: effects on adhesion molecules and CD40–CD40L system

The vascular effects of nitrolinoleate (LNO₂), an endogenous product of linoleic acid (LA) nitration by nitric oxide-derived species and a potential nitrosating agent, were investigated on rat endothelial-leukocyte interactions. Confocal microscopy analysis demonstrated that LNO₂ was capable to deliver free radical nitric oxide (^·NO) into cells, 5 min after its administration to cultured cells, with a peak of liberation at 30 min. THP-1 monocytes incubated with LNO₂ for 5 min presented nitrosation of CD40, leading to its inactivation. Other anti-inflammatory actions of LNO₂ were observed in vivo by intravital microscopy assays. LNO₂ decreased the number of adhered leukocytes in postcapillary venules of the mesentery network. In addition to this, LNO₂ reduced mRNA and protein expression of β2-integrin in circulating leukocytes, as well as VCAM-1 in endothelial cells isolated from postcapillary venules, confirming its antiadhesive effects on both cell types. Moreover, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, partially abolished the inhibitory action of LNO₂ on leukocyte-endothelium interaction, suggesting that the antiadhesion effects of LNO₂ involve a dual role in leukocyte adhesion, acting as a nitric oxide donor as well as through nitric oxide-independent mechanisms. In conclusion, LNO₂ inhibited adhesion molecules expression and promoted ^·NO inactivation of the CD40–CD40L system, both important processes of the inflammatory response.     

Identification of CD3ε, CD4, CD8β splice variants of Atlantic salmon

In vertebrates, CD3 complex and CD4 and CD8 co-receptors are essential for signal transduction during T cell activation. In the present study, we report the mRNA spliced variants of the Atlantic salmon CD3ε, CD4 and CD8β and the effect of pathogen encounter on the expression of these variants. CD3ε is alternatively spliced in thymus, head kidney, spleen and gills to give rise to the complete mRNA sequence and to an alternative product that lacks the transmembrane exon. CD4 is also alternatively spliced in the thymus, head kidney, spleen and gills to form two variants, although the alternative product is barely detectable. The alternative product lacks the exon 1B encoding the D1 domain, which is essential for binding to MHC class II proteins. Two amplicons were also found for the CD8β gene; sequencing analysis revealed that the main PCR product corresponds to the previously reported CD8β sequence, whereas the variant sequence encodes a potential protein that lacks the Ig-like domain. The expression of CD3, CD4, CD8β genes also analyzed in head kidney of LPS-treated and IPNV infected salmon and different patterns of expression were observed. The presence and balance of the different variants of T cell co-receptors could be related to the ability of fish to induce a particular type of immune response, as well as, the ability of the pathogen to modify the fish immune response.