Functional role of the nicotinic arm of the acetylcholine regulatory axis in human B-cell lines.
Functional role of the nicotinic arm of the acetylcholine regulatory axis in human B-cell lines.
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DOI：
10.2147/jep.s7055
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发表时间：
2009
影响因子：
--
通讯作者：
Grando SA
中科院分区：
文献类型：
--
作者：
Arredondo J;Omelchenko D;Chernyavsky AI;Qian J;Skok M;Grando SA
我们研究了烟碱型乙酰胆碱受体（nAChRs）参与人类B细胞系的炎症相关活动。在Daudi细胞中，用地棘蛙素激活nAChR在mRNA和蛋白水平上消除了促炎标志物考克斯-2的泛山梨醇依赖性上调，表明烟碱能信号传导抑制B细胞活化。虽然对B细胞的抗炎作用主要是通过α7 nAChR介导的，但可以从甲基灰乌头碱消除地棘蛙素效应来判断，α7和非α7 nAChR（如含α2受体）均参与B细胞凋亡的调节。净效应是抗凋亡。为了确定nAChR在调节B细胞活化/浆细胞分化中的作用，我们测量了CD 38、CD 138和Bcl-6基因表达的变化。地棘蛙素在转录水平显著上调CD 38（P < 0.05），在翻译水平显著上调CD 138和Bcl-6 -。AR-R17779可显著提高CD 38和CD 138蛋白水平（P < 0.05）。在这两种情况下，地棘蛙素的效果被废除与Mec，和AR-R17779 -的MLA，证明了nAChRs在调节Daudi细胞分化的功能作用。所获得的结果揭示了α7和非α7 nAChRs对B细胞活化/分化的调节的不同贡献，并表明通过乙酰胆碱调节轴的烟碱臂的信号传导对于B细胞参与炎症是重要的。
We studied the involvement of nicotinic acetylcholine receptors (nAChRs) in the inflammation-related activity of human B-cell lines. Activation of nAChRs in Daudi cells with epibatidine abolished the pansorbin-dependent upregulation of the pro-inflammatory marker Cox-2 both at the mRNA and protein levels, indicating that the nicotinergic signaling suppresses B-cell activation. While the anti-inflammatory action on B-cells was mediated predominantly through α7 nAChR, as could be judged from abolishing epibatidine effects with methyllycaconitine, both α7 and non-α7 nAChRs, such as α2-containing receptors, were involved in regulation of B-cell apoptosis. The net effect was antiapoptotic. To determine the role of nAChRs in regulating B-cell activation/plasmacytic differentiation, we measured changes in the CD38, CD138 and Bcl-6 gene expression. Epibatidine significantly (P < 0.05) upregulated CD38 at the transcriptional level and CD138 and Bcl-6 – at the translational levels. AR-R17779 significantly (P < 0.05) increased the protein levels of CD38 and CD138. In both cases, the effect of epibatidine was abolished with Mec, and that of AR-R17779 – by MLA, demonstrating a functional role of nAChRs in regulating Daudi cell differentiation. The obtained results revealed distinct contributions of α7 and non-α7 nAChRs to regulation of B-cell activation/differentiation, and suggested that signaling through the nicotinic arm of acetylcholine regulatory axis is important for B-cell involvement in inflammation.