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

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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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)

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 and 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:

10 Nov 2020 08:04

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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