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c-Jun N-Terminal Kinase as a Therapeutic Target in Experimental Autoimmune Encephalomyelitis

1
Department of Neurology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
2
Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland
3
Graduate School for Cellular and Biomedical Sciences, University of Bern, 3010 Bern, Switzerland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(10), 2154; https://doi.org/10.3390/cells9102154
Received: 3 September 2020 / Accepted: 16 September 2020 / Published: 23 September 2020
c-Jun N-terminal kinase (JNK) is upregulated during multiple sclerosis relapses and at the peak of experimental autoimmune encephalomyelitis (EAE). We aim to investigate the effects of pharmacological pan-JNK inhibition on the course of myelin oligodendrocyte glycoprotein (MOG35-55) EAE disease using in vivo and in vitro experimental models. EAE was induced in female C57BL/6JRj wild type mice using MOG35-55. SP600125 (SP), a reversible adenosine triphosphate competitive pan-JNK inhibitor, was then given orally after disease onset. Positive correlation between SP plasma and brain concentration was observed. Nine, but not three, consecutive days of SP treatment led to a significant dose-dependent decrease of mean cumulative MOG35-55 EAE severity that was associated with increased mRNA expression of interferon gamma (INF-γ) and tumor necrosis factor alpha (TNF-α) in the spinal cord. On a histological level, reduced spinal cord immune cell-infiltration predominantly of CD3+ T cells as well as increased activity of Iba1+ cells were observed in treated animals. In addition, in vitro incubation of murine and human CD3+ T cells with SP resulted in reduced T cell apoptosis and proliferation. In conclusion, our study demonstrates that pharmacological pan-JNK inhibition might be a treatment strategy for autoimmune central nervous system demyelination. View Full-Text
Keywords: multiple sclerosis; immunotherapy; mitogen-activated protein kinases; MAPK; SP600125; neuroinflammation multiple sclerosis; immunotherapy; mitogen-activated protein kinases; MAPK; SP600125; neuroinflammation
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MDPI and ACS Style

Bagnoud, M.; Briner, M.; Remlinger, J.; Meli, I.; Schuetz, S.; Pistor, M.; Salmen, A.; Chan, A.; Hoepner, R. c-Jun N-Terminal Kinase as a Therapeutic Target in Experimental Autoimmune Encephalomyelitis. Cells 2020, 9, 2154. https://doi.org/10.3390/cells9102154

AMA Style

Bagnoud M, Briner M, Remlinger J, Meli I, Schuetz S, Pistor M, Salmen A, Chan A, Hoepner R. c-Jun N-Terminal Kinase as a Therapeutic Target in Experimental Autoimmune Encephalomyelitis. Cells. 2020; 9(10):2154. https://doi.org/10.3390/cells9102154

Chicago/Turabian Style

Bagnoud, Maud; Briner, Myriam; Remlinger, Jana; Meli, Ivo; Schuetz, Sara; Pistor, Maximilian; Salmen, Anke; Chan, Andrew; Hoepner, Robert. 2020. "c-Jun N-Terminal Kinase as a Therapeutic Target in Experimental Autoimmune Encephalomyelitis" Cells 9, no. 10: 2154. https://doi.org/10.3390/cells9102154

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