Experimental autoimmune encephalomyelitis: Association with mutual regulation of RelA (p65)/NF-κB and phospho-IκB in the CNS

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• 作者：Insun Hwang^a ; Danbee Ha^a ; Ginnae Ahn^b ; Eunjin Park^a ; Haejin Joo^a ; Youngheun Jee^a ; ^{yhjee@jejunu.ac.kr" rel="nofollow}
• 关键词：Experimental autoimmune encephalomyelitis ; RelA (p65) ; Phospho-I&#x3ba ; B ; TPCK
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：29 July 2011
• 年：2011
• 卷：411
• 期：2
• 页码：464-470
• 全文大小：1056 K

文摘

Recently emerging evidence that the NF-κB family plays an important role in autoimmune disease has produced very broad and sometimes paradoxical conclusions. In the present study, we elucidated that the activation of RelA (p65) of NF-κB and IκB dissociation assumes a distinct role in experimental autoimmune encephalomyelitis (EAE) progression by altering IκB phosphorylation and/or degradation. In the present study of factors that govern EAE, the presence and immunoreactivity of nuclear RelA and phospho-IκB were recorded at the initiation and peak stage, and degradation of IκBα progressed rapidly at an early stage then stabilized during recovery. The immunoreactivity to RelA and phospho-IκB occurred mainly in inflammatory cells and microglial cells but only slightly in astrocytes. Subsequently, the blockade of IκB dissociation from NF-κB reduced the severity of disease by decreasing antigen-specific T cell response and production of IL-17 in EAE. Thus, blocking the dissociation of IκB from NF-κB can be utilized as a strategy to inhibit the NF-κB signal pathway thereby to reduce the initiation, progression, and severity of EAE.