The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis
AbstractExtracellular signal-regulated kinase (ERK) signaling plays a crucial role in regulating immune cell function and has been implicated in autoimmune disorders. To date, all commercially available inhibitors of ERK target upstream components, such as mitogen-activated protein (MAP) kinase/ERK kinase (MEKs), but not ERK itself. Here, we directly inhibit nuclear ERK translocation by a novel pharmacological approach (Glu-Pro-Glu (EPE) peptide), leading to an increase in cytosolic ERK phosphorylation during T helper (Th)17 cell differentiation. This was accompanied by diminished secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine influencing the encephalitogenicity of Th17 cells. Neither the production of the cytokine interleukin (IL)-17 nor the proliferation rate of T cells was affected by the EPE peptide. The in vivo effects of ERK inhibition were challenged in two independent variants of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Overall, ERK inhibition had only a very minor impact on the clinical disease course of EAE. This indicates that while ERK translocation might promote encephalitogenicity in T cells in vitro by facilitating GM-CSF production, this effect is overcome in more complex in vivo animal models of central nervous system (CNS) autoimmunity. View Full-Text
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Birkner, K.; Wasser, B.; Loos, J.; Plotnikov, A.; Seger, R.; Zipp, F.; Witsch, E.; Bittner, S. The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis. Int. J. Mol. Sci. 2017, 18, 1990.
Birkner K, Wasser B, Loos J, Plotnikov A, Seger R, Zipp F, Witsch E, Bittner S. The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis. International Journal of Molecular Sciences. 2017; 18(9):1990.Chicago/Turabian Style
Birkner, Katharina; Wasser, Beatrice; Loos, Julia; Plotnikov, Alexander; Seger, Rony; Zipp, Frauke; Witsch, Esther; Bittner, Stefan. 2017. "The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis." Int. J. Mol. Sci. 18, no. 9: 1990.
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