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(10) MDPI 10.3390/cells9102154
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Bagnoud, 2020, c_Jun N_Terminal Kinase.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (4MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Sahli Building > Forschungsgruppe Neurologie 04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Bagnoud, Maud Marie, Briner, Myriam Sandra, Remlinger, Jana Silke, Meli, Ivo Maurice, Pistor, Maximilian, Salmen, Anke, Chan, Andrew Hao-Kuang, Hoepner, Robert |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2073-4409 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Chantal Kottler |
Date Deposited: |
10 Nov 2020 08:04 |
Last Modified: |
05 Dec 2022 15:41 |
Publisher DOI: |
10.3390/cells9102154 |
PubMed ID: |
32977663 |
Uncontrolled Keywords: |
MAPK SP600125 immunotherapy mitogen-activated protein kinases multiple sclerosis neuroinflammation |
BORIS DOI: |
10.7892/boris.147418 |
URI: |
https://boris.unibe.ch/id/eprint/147418 |
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