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

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
Shivaprasad H Venkatesha, Kamal D Moudgil

Abstract

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. 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. 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...Continue Reading

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Citations

Nov 20, 2019·Journal of Cellular and Molecular Medicine·Yuqin WangZhaoguo Liu
Aug 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shuyu ZhanJeffrey Wang
Apr 18, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xue BaiYu-Ping Tang
Jun 8, 2021·Frontiers in Molecular Neuroscience·Baowen LiuGuangyou Duan
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stefania SchiavoneLuigia Trabace

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Methods Mentioned

BETA
PCR
FCS
flow cytometry

Software Mentioned

FCS Express
Molecular activity
Ingenuity Pathway Analysis ( IPA )
Ingenuity pathway analysis ( IPA

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