Enhanced serum antigen-specific IgG1 and proinflammatory cytokine production in nicotinic acetylcholine receptor α7 subunit gene knockout mice
Enhanced serum antigen-specific IgG1 and proinflammatory cytokine production in nicotinic acetylcholine receptor α7 subunit gene knockout mice
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DOI：
10.1016/j.jneuroim.2007.07.003
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发表时间：
2007-09-01
影响因子：
3.3
通讯作者：
Kawashima, Koichiro
中科院分区：
文献类型：
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作者：
Fujii, Yoshihito X.;Fujigaya, Hirofumi;Kawashima, Koichiro
人和小鼠的免疫细胞，如主要由T细胞和B细胞组成的单核白细胞，骨髓来源的树突状细胞（dc）和巨噬细胞都表达各种烟碱乙酰胆碱受体（nAChR）亚基。活化的T细胞和dc具有通过胆碱乙酰转移酶合成ACh的能力，提示免疫细胞中表达的非神经元胆碱能系统在调节免疫细胞功能中的作用。用尼古丁刺激人白血病T和B细胞系引起短暂的Ca2+信号，该信号被a-bungarotoxin拮抗，表明α 7亚基参与其中。此外，α 7 nachr已被证明负性调节巨噬细胞中肿瘤坏死因子(TNF)- α的合成和释放。这些发现表明免疫细胞的功能是由其自身的非神经元胆碱能系统调节的，至少部分是通过α 7 nachr介导的途径。在本研究中，我们通过测定nAChR α 7亚基基因敲除（α 7 KO）和野生型C57BL/6J小鼠免疫后激活的脾脏细胞中tnf - α、γ干扰素（ifn - γ）和白细胞介素(IL)-6的产生，检测α 7 nAChRs在免疫功能调节中的作用。我们发现U7 KO小鼠血清总IgG和抗ova特异性IgG(1)水平显著升高，尽管两种基因型之间血清总IgG和抗ova特异性IgM水平无显著差异。α 7 KO小鼠脾脏细胞中tnf - α、ifn - γ和IL-6的产生显著促进。AChE mRNA的表达在两种基因型间无明显差异。这些结果表明，α - 7 nAChRs参与细胞因子的产生，通过调节tnf - α、ifn - γ和IL-6的产生，导致抗体产生的修饰，但不参与免疫细胞中胆碱能成分的表达。(C) 2007 Elsevier B.V.版权所有
Human and murine immune cells such as mononuclear leukocytes consisting of mainly T and B cells, bone marrow derived dendritic cells (DCs) and macrophages all express various nicotinic acetylcholine (ACh) receptor (nAChR) subunits. Activated T cells and DCs have the ability to synthesize ACh by choline acetyltransferase, suggesting the role of non-neuronal cholinergic system expressed in immune cells in the regulation of immune cell function. Stimulation of human leukemic T and B cell lines with nicotine causes a transient Ca2+-signaling that is antagonized by a-bungarotoxin, suggesting the involvement of alpha 7 subunit. Furthermore, alpha 7 nAChRs have been shown to negatively regulate synthesis and release of tumor necrosis factor (TNF)-alpha in macrophages. These findings suggest that immune cell function is regulated by its own non-neuronal cholinergic system, at least in part, via alpha 7 nAChR-mediated pathways. In the present study, we tested the role of alpha 7 nAChRs in the regulation of immune function by measuring total serum and antigen-specific IgG(1) and IgM, and production of TNF-alpha, gamma interferon (IFN-gamma) and interleukin (IL)-6 in activated spleen cells of nAChR alpha 7 subunit gene knockout (alpha 7 KO) and wild-type C57BL/6J mice immunized with ovalbumin (OVA). We found that serum levels of total and anti-OVA-specific IgG(1) were significantly elevated in U7 KO mice, though there were no significant differences in serum levels of total and anti-OVA-specific IgM between the two genotypes. Production of TNF-alpha, IFN-gamma and IL-6 in spleen cells was significantly facilitated in alpha 7 KO mice. Expression of AChE mRNA was not different between the two genotypes. These results suggest that alpha 7 nAChRs are involved in the regulation of cytokine production, through which modulates TNF-alpha, IFN-gamma and IL-6 productions, leading to modification of antibody production, but are not involved in expression of cholinergic components in immune cells. (C) 2007 Elsevier B.V. All rights reserved.