Gveric D, Kaltschmidt C, Cuzner M L, Newcombe J
Multiple Sclerosis Laboratory, Institute of Neurology, London, England.
J Neuropathol Exp Neurol. 1998 Feb;57(2):168-78. doi: 10.1097/00005072-199802000-00008.
NF-kappaB is a transcription factor family which on translocation to the nucleus regulates gene expression during cell activation. As such, NF-kappaB may play a role in the microglial response to myelin damage in multiple sclerosis (MS) lesions. Here the cellular localization of NF-kappaB and expression of the inhibitory I kappaBalpha were examined by immunocytochemistry on central nervous system (CNS) tissue from MS and control cases. In normal control white matter, the active form of the NF-kappaB subunit RelA (p65) was localized in microglial nuclei, while the c-Rel and p50 subunits and the inhibitory I kappaBalpha were restricted to the cytoplasm. In contrast, in actively demyelinating plaques, the RelA, c-Rel, and p50 subunits of NF-kappaB and I kappaBalpha were all present in macrophage nuclei in both parenchymal and perivascular areas. RelA was also found in the nuclei of a subset of hypertrophic astrocytes. Only c-Rel had a nuclear localization in lymphocytes in perivascular inflammatory cuffs. Our results suggest that constitutive activation of the RelA subunit in the nuclei of resting microglia may facilitate a rapid response to pathological stimuli in the CNS. Activation of the inducible NF-kappaB pool in macrophages in MS lesions could amplify the inflammatory reaction through upregulation of NF-kappaB-controlled adhesion molecules and cytokines.
核因子-κB是一个转录因子家族，其转位至细胞核后可在细胞激活过程中调节基因表达。因此，核因子-κB可能在多发性硬化症（MS）病灶中，小胶质细胞对髓鞘损伤的反应中发挥作用。在此，通过免疫细胞化学方法，对来自MS患者及对照病例的中枢神经系统（CNS）组织，检测了核因子-κB的细胞定位及抑制性IκBα的表达。在正常对照白质中，核因子-κB亚基RelA（p65）的活性形式定位于小胶质细胞核，而c-Rel和p50亚基以及抑制性IκBα则局限于细胞质。相比之下，在活动性脱髓鞘斑块中，核因子-κB的RelA、c-Rel和p50亚基以及IκBα均存在于实质和血管周围区域的巨噬细胞核中。RelA也见于一部分肥大星形胶质细胞的细胞核中。仅c-Rel在血管周围炎性套袖中的淋巴细胞细胞核中有定位。我们的结果提示，静息小胶质细胞核中RelA亚基的组成性激活可能有助于对CNS中的病理刺激做出快速反应。MS病灶中巨噬细胞中可诱导性核因子-κB池的激活可通过上调核因子-κB控制的黏附分子和细胞因子来放大炎症反应。
