scholarly journals Posttranscriptional Gene Regulation of IL-17 by the RNA-Binding Protein HuR Is Required for Initiation of Experimental Autoimmune Encephalomyelitis

2013 ◽  
Vol 191 (11) ◽  
pp. 5441-5450 ◽  
Author(s):  
Jing Chen ◽  
Jason Cascio ◽  
Joseph D. Magee ◽  
Patsharaporn Techasintana ◽  
Matthew M. Gubin ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Autoimmune Encephalomyelitis ◽  
Posttranscriptional Gene Regulation ◽  
Experimental Autoimmune

scholarly journals Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis

2020 ◽  
Author(s):  
Vittoria Borgonetti ◽  
Maria Domenica Sanna ◽  
Laura Lucarini ◽  
Nicoletta Galeotti
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Rna Binding ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Rna Binding Protein ◽  
Motor Dysfunction ◽  
Autoimmune Encephalomyelitis ◽  
Activated Microglia ◽  
Experimental Autoimmune

AbstractMultiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalomyelitis (EAE) in mice, by focusing on HuR, an RNA-binding protein involved in inflammatory and immune phenomena. Spinal cord sections of EAE mice showed an increased HuR immunostaining that was abundantly detected in the cytoplasm of activated microglia, a pattern associated with its increased activity. Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) decreased the proinflammatory activated microglia, inflammatory infiltrates, and the expression of the proinflammatory cytokines IL-1β, TNF-α, and IL-17, and inhibited the activation of the NF-κB pathway. The beneficial effect of anti-HuR ASO in EAE mice corresponded also to a decreased permeability of the blood–brain barrier. EAE mice showed a reduced spinal CD206 immunostaining that was restored by anti-HuR ASO, indicating that HuR silencing promotes a shift to the anti-inflammatory and regenerative microglia phenotype. Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss. Targeting HuR might represent an innovative and promising perspective to control neurological disturbances in MS patients.

scholarly journals Role of the RNA-Binding Protein Tristetraprolin in Glucocorticoid-Mediated Gene Regulation

2008 ◽  
Vol 180 (12) ◽  
pp. 8342-8353 ◽  
Author(s):  
Faoud T. Ishmael ◽  
Xi Fang ◽  
Maria Rosaria Galdiero ◽  
Ulus Atasoy ◽  
William F. C. Rigby ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein
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