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Inflammation Research
Erschienen in: Inflammation Research 4/2019

28.02.2019 | Original Research Paper

Celastrol suppresses experimental autoimmune encephalomyelitis via MAPK/SGK1-regulated mediators of autoimmune pathology

verfasst von: Shivaprasad H. Venkatesha, Kamal D. Moudgil

Erschienen in: Inflammation Research | Ausgabe 4/2019

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Abstract

Objective and design

Multiple sclerosis (MS) is a debilitating autoimmune disease involving immune dysregulation of the pathogenic T helper 17 (Th17) versus protective T regulatory (Treg) cell subsets, besides other cellular aberrations. Studies on the mechanisms underlying these changes have unraveled the involvement of mitogen-activated protein kinase (MAPK) pathway in the disease process. We describe here a gene expression- and bioinformatics-based study showing that celastrol, a natural triterpenoid, acting via MAPK pathway regulates the downstream genes encoding serum/glucocorticoid regulated kinase 1 (SGK1), which plays a vital role in Th17/Treg differentiation, and brain-derived neurotrophic factor (BDNF), which is a neurotrophic factor, thereby offering protection against experimental autoimmune encephalomyelitis (EAE) in mice.

Methods

We first tested the gene expression profile of splenocytes of EAE mice in response to the disease-related antigen, myelin oligodendrocyte glycoprotein (MOG), and then examined the effect of celastrol on that profile.

Results

Interestingly, celastrol reversed the expression of many MOG-induced genes involved in inflammation and immune pathology. The MAPK pathway involving p38MAPK and ERK was identified as one of the mediators of celastrol action. It involved suppression of SGK1 but upregulation of BDNF, which then contributed to protection against EAE.

Conclusion

Our results not only provide novel insights into disease pathogenesis, but also offer promising therapeutic targets for MS.
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Metadaten
Titel
Celastrol suppresses experimental autoimmune encephalomyelitis via MAPK/SGK1-regulated mediators of autoimmune pathology
verfasst von
Shivaprasad H. Venkatesha
Kamal D. Moudgil
Publikationsdatum
28.02.2019
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 4/2019
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-019-01219-x

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