A role for calcitonin gene related peptide (CGRP) in the regulation of early B lymphocyte differentiation.
A role for calcitonin gene related peptide (CGRP) in the regulation of early B lymphocyte differentiation.
复制标题
降钙素基因相关肽 (CGRP) 在调节早期 B 淋巴细胞分化中的作用。
DOI：
10.1139/y95-150
复制
发表时间：
1995
影响因子：
2.1
通讯作者：
Ciallella,JR
中科院分区：
文献类型：
--
作者：
McGillis,JP;Rangnekar,V;Ciallella,JR
在以前的研究中，我们确定了降钙素基因相关肽（CGRP）的高亲和力腺苷酸环化酶连接受体在大鼠T和B细胞，淋巴细胞系，包括小鼠前B细胞系70 Z/3，和小鼠骨髓细胞。CGRP对早期B细胞分化的影响已经使用70 Z/3细胞系进行了检查。CGRP抑制脂多糖（LPS）诱导70 Z/3细胞表面免疫球蛋白（s IG）蛋白表达，这种作用与IG重链（μ）和轻链（κ）mRNA稳态水平降低相关。在这份报告中，实验描述，CGRP抑制sIg表达的机制提供了进一步的信息。在70 Z/3细胞中检查了CGRP抑制LPS诱导的sIg表达的动力学。CGRP对sIg诱导的抑制作用的最佳窗口发生在细胞用LPS处理后至少24小时。 为了确定CGRP对sIg表达的抑制作用是否是通过抑制NFκ-B易位到细胞核来介导的，使用来自70 Z/3细胞的核蛋白进行电泳迁移率变动分析。在用LPS或LPS + CGRP处理的细胞中，NFκ-B结合活性没有差异，表明CGRP的抑制作用不是通过抑制NFκ-B活性介导的。这些研究进一步证明CGRP在早期B细胞分化中起抑制作用。最后，提出了一个模型，描述了一个集成的作用，CGRP在稳态调节早期B细胞differentiation. Keywords：神经肽，免疫，免疫球蛋白，神经免疫学，降钙素基因相关肽。
In previous studies we identified high affinity adenylyl cyclase linked receptors for calcitonin gene related peptide (CGRP) on rat T and B cells, on lymphocyte cell lines including the mouse pre-B cell line 70Z/3, and on cells in mouse bone marrow. The effect of CGRP on early B cell differentiation has been examined using the 70Z/3 cell line. CGRP inhibits the lipopolysaccharide (LPS) induction of surface immunoglobulin (sIg) protein expression in 70Z/3 cells, an effect that is associated with a decrease in the steady-state levels of Ig heavy (μ) and light (κ) chain mRNA. In this report, experiments are described that provide further information on the mechanism by which CGRP inhibits sIg expression. The kinetics of CGRP inhibition of LPS-induced sIg expression was examined in 70Z/3 cells. An optimal window for the inhibitory effect of CGRP on sIg induction occurs at least 24 h after the cells are treated with LPS. To determine whether the inhibitory effects of CGRP on sIg expression are mediated by an inhibition of NFκ-B translocation to the nucleus, electrophoretic mobility shift assays were performed using nuclear proteins from 70Z/3 cells. There was no difference in NFκ-B binding activity in cells that had been treated with LPS or LPS + CGRP, suggesting that the inhibitory effect of CGRP is not mediated by an inhibition of NFκ-B activity. These studies provide further evidence that CGRP plays an inhibitory role in early B cell differentiation. Finally, a model is proposed that describes an integrated role for CGRP in the homeostatic regulation of early B cell differentiation.Key words: neuropeptides, immune, immunoglobulin, neuroimmunology, calcitonin gene related peptides.