Glatiramer acetate inhibits the activation of NFκB in the CNS of experimental autoimmune encephalomyelitis
2011
Hwang, I.S., Jeju National University, Jeju, Republic of Korea | Ha, D.B., Jeju National University, Jeju, Republic of Korea | Kim, D.S., Jeju National University, Jeju, Republic of Korea | Joo, H.J., Jeju National University, Jeju, Republic of Korea | Jee, Y.H., Jeju National University, Jeju, Republic of Korea
Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B (NFκB) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, NFκB activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of NFκB activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of NFκB and phospho-IκB proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of NFκB and phospho-IκB significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of NFκB and phophorylation of IκB in the CNS. Subsequently, the inhibition of NFκB activation and IκB phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.
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