Immune response in the relapsing-remitting experimental autoimmune encephalomyelitis in mice: The role of the NF-κB signaling pathway.

Characteristics of the mouse model of relapsing-remitting experimental autoimmune encephalomyelitis (rEAE) closely resemble manifestations of multiple sclerosis in humans. In the present study， we investigated the mechanisms of inflammatory response， focusing on NF-κB pathway activation. Cytokine response in rEAE mice was multiphasic: the early phase was characterized by the increase in interferon-γ level in plasma. In the later stage， the level of interleukin-17， but not of interferon-γ， was increased. The early phase of rEAE was also accompanied by increased RelA/p65 phosphorylation at Ser276 in spleen cells， whereas the rEAE maintenance phase was characterized by RelA/p65 phosphorylation at Ser536 and IKK phosphorylation. The IKKα/β inhibitor reduced interleukin-17 and interferon-γ levels in plasma and alleviated rEAE symptoms. The IKKα/β inhibitor decreased IKK and p65(Ser536) phosphorylation， but doubled p65(Ser276) phosphorylation in rEAE mice. The increased RelA/p65(Ser276) phosphorylation coincided in time with the production of interferon-γ， Hsp72， and the early phase of IL-17 generation， whereas increased RelA/p65(Ser536) phosphorylation coincided with the activation of IKK， SAPK/JNK， and p53， as well as the late phase of IL-17 production， indicating the role of the RelA/p65 phosphorylation events in the induction and maintenance of rEAE.