生物活性肽——蛋氨酸脑啡肽的免疫

源自肾上腺前脑啡肽原的具有吗啡样生物活性的内源性神经肽蛋氨酸脑啡肽(methionine enkephalin,MENK),由５个氨基酸残基Tyr Gly Gly Phe Met组成,与G蛋白偶联的７次跨膜特异性受体结合后发挥不同的生物学功能。目前,对蛋氨酸脑啡肽的作用及其机制研究已经取得了很大进展。本文就MENK对于免疫系统的调节及其对肿瘤、自身免疫病、艾滋病等免疫系统相关疾病的治疗作用予以综述。     

Functional modulation of the pathway between dendritic cells (DCs) and CD4+T cells by the neuropeptide: methionine enkephalin (MENK)

MENK, the endogenous neuropeptide, is suggested to be involved in the regulatory loop between the immune and neuroendocrine systems, with modulation of various functions of cells related to both the innate and adaptive immune systems. Our present research findings show that MENK serves as an immune modulator to the pathway between DCs and CD4+T cells. We studied changes of DCs in key surface molecules, the activity of acid phosphatases (ACPs), the production of IL-12, and the effects on murine CD4+T cell expansion and their cytokine production by MENK alone, and in combination with interkeukin-2 (IL-2) or interferon-γ (IFN-γ). In fact, we found that MENK could markedly induce the maturation of DCs through the addition of surface molecules such as MHC class II, CD86, and CD40 on murine DCs, the production of IL-12, and the down-regulation of ACP inside DCs, (which occurs when phagocytosis of DCs is decreased, and antigen presentation increased with maturation). We also found that MENK alone or in combination with IL-2 or IFN-γ, could markedly up-regulate both CD4+T cell expansion and the CD4 molecule expression in vivo and in vitro and that MENK alone, or MENK + IL-2, could enhance the production of interferon-γ from CD4+T cells. Moreover, MENK alone, or MENK + IFN-γ, could enhance the production of IL-2 from CD4+T cells. It is therefore concluded that MENK can exert positive modulation to the pathway between dendtritic cells and CD4+T cells.     

生物肽-蛋氨酸脑啡肽增强树突状细胞抗肿瘤活性研究

采用反复冻融法制备Rac-1淋巴瘤细胞总抗原,与树突状细胞（DC2.4）共培养制备DC瘤苗;设置不同实验组,M组及RM组加入蛋氨酸脑啡肽（MENK）,研究MENK对DC瘤苗抗肿瘤细胞的杀伤活性影响。结果表明：MENK作用于DC瘤苗后,DC2.4形态上更趋向于成熟,且CD86、MHC-Ⅱ类分子表达水平与对照组相比较明显升高;DC2.4酸性磷酸酶（ACP）含量与对照组相比较明显减少而IL-12的分泌水平升高;同时,DC2.4诱导淋巴细胞增殖能力增强,且诱导活化的淋巴细胞对Rac-1淋巴瘤细胞的杀伤活性与对照组相比较明显增强。结果可见,MENK可明显促进特异性负载Rac-1淋巴瘤抗原的DC2.4的成熟,并增强特异性诱导活化的淋巴细胞对Rac-1淋巴瘤细胞的杀伤活性。     

蛋氨酸脑啡肽—阿片受体激活免疫细胞抗肿瘤活性的研究进展

蛋氨酸脑啡肽(MENK)是人体中的一种神经递质,其阿片受体广泛存在于免疫细胞表面。MENK与阿片受体相结合,通过调节cAMP-PKA信号通路、Ca2+-钙调蛋白、蛋白激酶C等多种物质的表达,参与到免疫细胞的成熟分化。进一步研究提示,适当剂量的MENK通过激活T细胞、NK细胞、LAK细胞等发挥抗肿瘤的作用。此外,MENK-阿片生长因子受体(OGFr)通路的过表达,直接抑制肿瘤发展与血管生长。     

肠道菌群对蛋氨酸脑啡肽治疗肿瘤疗效的影响

蛋氨酸脑啡肽(Methionine enkephalin,MENK)是一种内源性阿片肽,有良好的抗肿瘤作用,而肠道菌群对MENK抗肿瘤作用的影响尚不清楚.本研究建立小鼠肠道菌群紊乱模型及荷瘤小鼠模型,以16s rRNA测序法检测肠道菌群丰度、监测小鼠体重、绘制肿瘤生长曲线,以流式细胞术检测小鼠肿瘤浸润CD4+T细胞、C...     

蛋氨酸脑啡肽抑制人胃癌细胞BGC823增殖作用及免疫调节机制

采用不同浓度梯度的蛋氨酸脑啡肽(methionine enkephalin,MENK)体外作用于人胃癌细胞BGC823后,探讨对其增殖影响及其作用机制,为胃癌的免疫治疗提供理论依据。体外培养人胃癌细胞株BGC823,PCR检测阿片受体OGFr的表达;用不同浓度(0、1、2、3、4 mg/mL)的MENK体外作用于BGC823细胞24、48、72、96 h后,MTS检测MENK对其增殖影响;流式细胞术和Annexin V-FITC/PI双染法检测4 mg/mL MENK体外处理48、72 h后BGC823细胞凋亡变化。结果显示,人胃癌BGC823细胞有阿片受体OGFr的表达;MENK可抑制BGC823细胞增殖,且随着剂量的增加和时间的延长,其抑制作用逐渐增强(P0.05);4 mg/mL MENK48 h处理组与空白组相比细胞凋亡率增加,72 h处理组与48 h处理组结果一致(P0.05)。结果表明,MENK可抑制BGC823细胞增殖,具有显著的剂量依赖性和时间依赖性,且可通过诱导细胞凋亡抑制BGC823细胞的增殖。