Expression of activity-dependent neuroprotective protein in the immune system: possible functions and relevance to multiple sclerosis.

Expression of activity-dependent neuroprotective protein in the immune system: possible functions and relevance to multiple sclerosis.
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DOI:
10.1159/000258695
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发表时间:
2010
影响因子:
2.4
通讯作者:
Constantinescu CS
Constantinescu CS
中科院分区:
医学4区
文献类型:
--
作者:
Braitch M;Kawabe K;Nyirenda M;Gilles LJ;Robins RA;Gran B;Murphy S;Showe L;Constantinescu CS

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活动依赖性神经保护剂(ADNP)是一种神经保护分子,含有8个氨基酸的肽NAPVSIPQ(NAP),足以发挥其神经保护作用。评估ADNP在正常人和多发性硬化患者免疫系统中的表达。使用抗ADNP(NAP)抗体和T细胞、B细胞、单核细胞和自然杀伤细胞的标记物染色,评估来自健康供体和多发性硬化(MS)患者的外周血单核细胞(PBMC)中的ADNP表达。在MS患者(n = 24)和匹配对照(n = 21)的外周血中测定ADNP mRNA。在刺激的PBMC中通过流式细胞术评估活化标志物⑶ 69和⑶ 154以及IFN-γ的表达。用氚标记胸苷掺入法检测NAP对免疫细胞增殖的影响。单核细胞、B细胞和T细胞表达ADNP,但调节性(CD 4 + CD 25+)T细胞不表达。NAP肽可降低PBMC中CD 69、CD 154和IFN-γ的表达,并抑制抗CD 3/抗CD 28刺激的PBMC增殖。与对照外周血相比,MS中ADNP mRNA降低。ADNP在许多免疫系统细胞中表达。MS患者PBMC中ADNP mRNA表达减少。NAP肽在神经保护中起重要作用,具有潜在的免疫调节特性。
Activity-dependent neuroprotector (ADNP) is a neuroprotective molecule containing an 8-amino acid peptide, NAPVSIPQ (NAP), that is sufficient for its neuroprotective effects. To assess the expression of ADNP in the human immune system in normal subjects and multiple sclerosis patients. ADNP expression was assessed in peripheral blood mononuclear cells (PBMCs) from healthy donors and multiple sclerosis (MS) patients using staining with anti-ADNP (NAP) antibodies and markers for T cells, B cells, monocytes and natural killer cells. ADNP mRNA was determined in peripheral blood from MS patients (n = 24) and matched controls (n = 21). Expression of activation markers CD69 and CD154 and of IFN-γ was assessed by flow cytometry in stimulated PBMCs. Effects of NAP on immune cell proliferation was assessed by tritiated thymidine incorporation. Monocytes, B cells and T cells, but not regulatory (CD4+CD25+) T cells expressed ADNP. NAP peptide decreased the expression of CD69, CD154 and IFN-γ in PBMC and caused suppressed anti-CD3-/anti-CD28-stimulated PBMC proliferation. ADNP mRNA was reduced in MS compared to control peripheral blood. ADNP is expressed in many immune system cells. ADNP mRNA is reduced in PBMCs in MS. The peptide NAP, which plays an important role in neuroprotection, has potential immunomodulatory properties.
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