Sublytic terminal complement complexes decrease P0 gene expression in Schwann cells
Sublytic terminal complement complexes decrease P0 gene expression in Schwann cells
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DOI：
10.1046/j.1471-4159.1999.0732321.x
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发表时间：
1999-12-01
影响因子：
4.7
通讯作者：
Koski, CL
中科院分区：
文献类型：
--
作者：
Dashiell, SM;Koski, CL
外周神经髓鞘上的补体级联激活可导致髓鞘破坏。虽然末端补体复合物（TCC）是瞬时检测雪旺细胞（SchCs）在炎症性神经病变，SchCs出现补体介导的溶解，并鲜为人知的是，亚溶解TCC沉积SchCs的功能后果。我们研究了亚溶补体在转录后和转录水平上调节髓鞘基因表达的作用。用致敏抗体（Ab）和正常人血清（NHS）补体处理经刺激以表达蛋白零（P-0）的培养的SchCs。P-0 mRNA含量在12 h内下降71%。在放线菌素D，P-0的存在下，mRNA水平下降50%，孵育后与抗体加10%NHS超过6小时，与对照水平相比，这表明增强P-0 mRNA降解。这种降低部分反映了TCC的形成，因为Ab + C7耗尽的人血清（C7 dHS）的C7重建或由纯化组分组装的TCC分别比Ab + C7 dHS或热活化组分下调了53%和55%的P-0 mRNA。瞬时转染入SchCs的P-0启动子/荧光素酶报告基因构建体的表达在6 h时被亚裂解TCC降低70%，表明P-0基因转录也被抑制。c-jun mRNA在30 min内被溶解性TCC上调，然后P-0 mRNA表达降低。我们的数据表明，亚溶解补体激活SchCs可能有助于周围神经脱髓鞘的髓鞘形成和压实的重要基因的表达减少。
Complement cascade activation on peripheral nerve myelin can cause myelin destruction. Although terminal complement complexes (TCCs) are transiently detected on Schwann cells (SchCs) during inflammatory neuropathy, SchCs appear resistant to complement-mediated lysis, and little is known about the functional consequences of sublytic TCC deposition on SchCs. We studied the effects of sublytic complement in modulating myelin gene expression at the posttranscriptional and transcriptional levels. Cultured SchCs, stimulated to express protein zero (P-0), were treated with sensitizing antibody (Ab) and normal human serum (NHS) complement. P-0 mRNA content decreased by 71% during 12 h. In the presence of actinomycin D, P-0, mRNA levels declined 50% following incubation with Ab plus 10% NHS over 6 h, compared with control levels, suggesting enhanced P-0 mRNA degradation. The decreases, in part, reflected TCC formation because C7 reconstitution of Ab plus C7-depleted human serum (C7dHS) or TCCs assembled from purified components down-regulated P-0 mRNA 53 and 55% over that of Ab plus C7dHS or heat-activated components, respectively. Expression of a P-0 promoter/luciferase reporter construct transiently transfected into SchCs was reduced 70% by sublytic TCCs at 6 h, demonstrating that P-0 gene transcription was also inhibited. c-jun mRNA was up-regulated within 30 min by sublytic TCCs, before the reduction in P-0 mRNA expression. Our data suggest that sublytic complement activation on SchCs may contribute to peripheral nerve demyelination by decreasing expression of genes important in myelin formation and compaction.