title: Experimental autoimmune encephalomyelitis: association with mutual regulation of RelA (p65)/NF-κB and phospho-IκB in the CNS.
abstract: 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.
authors.affiliation: College of Veterinary Medicine and Applied Radiological Science Institute, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Insun
authors.initials: I
authors.lastname: Hwang
authors.forename: Danbee
authors.initials: D
authors.lastname: Ha
authors.forename: Ginnae
authors.initials: G
authors.lastname: Ahn
authors.forename: Eunjin
authors.initials: E
authors.lastname: Park
authors.forename: Haejin
authors.initials: H
authors.lastname: Joo
authors.forename: Youngheun
authors.initials: Y
authors.lastname: Jee
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D014108:Tosylphenylalanyl Chloromethyl Ketone; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; D010750:Phosphoproteins; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014108:Tosylphenylalanyl Chloromethyl Ketone; D051550:I-kappa B Kinase