Journal
CELLULAR IMMUNOLOGY
Volume 336, Issue -, Pages 20-27Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2018.12.003
Keywords
Relapsing-remitting experimental autoimmune encephalomyelitis; NF-kappa B; p65/RelA phosphorylation; Interleukin 17; Interferon-gamma
Categories
Funding
- Program of Russian Academy of Sciences [1.18]
- Russian Foundation for Basic Research [17-44-500047, 18-04-00091]
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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-kappa B pathway activation. Cytokine response in rEAE mice was multiphasic: the early phase was characterized by the increase in interferon-gamma level in plasma. In the later stage, the level of interleukin-17, but not of interferon-gamma, 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 IKK alpha/beta inhibitor reduced interleukin-17 and interferon-y levels in plasma and alleviated rEAE symptoms. The IKK alpha/beta 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-gamma, 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.
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