Fingolimod ameliorates chronic experimental autoimmune neuritis by modulating inflammatory cytokines and Akt/mTOR/NF-κB signaling.
Brain Behav
; 13(4): e2965, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36917739
ABSTRACT
OBJECTIVE:
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disease that targets the myelin sheaths of the peripheral nerves. Fingolimod is a sphingosine 1 phosphate (S1P) receptor antagonist with a high affinity for S1P receptors through the Akt-mTOR pathway, and prior research has suggested that it might be helpful in autoimmune illnesses.METHODS:
Chronic experimental autoimmune neuritis (c-EAN) was induced by immunizing Lewis rats with the S-palm P0(180-199) peptide, and then the treatment group was intraperitoneally injected with fingolimod (1 mg/kg) daily. Hematoxylin and eosin staining was used to assess the severity of nerve injury. Immunohistochemistry staining showed that fingolimod's anti-inflammatory effects on c-EAN rats might be realized through the NF-κB signaling pathway. Tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-1beta (IL-1ß), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) were measured to evaluate the inflammation levels, and pAkt, p-S6, and p-p65 were used to measure the abundance of downstream activation markers to determine whether the Akt/mTOR/NF-κB signaling pathway was activated in the c-EAN model.RESULTS:
Fingolimod treatment reduced the inflammatory reaction and the expression of NF-κB in sciatic nerves. It also decreased the mRNA levels of the proinflammatory cytokines TNF-α, IFN-γ, IL-1ß, IL-6, iNOS, and ICAM-1 and pAkt, p-S6, and p-p65, representing the Akt/mTOR/NF-κB signaling pathway.CONCLUSION:
Our data showed that fingolimod could improve the disease course, alleviate the decrease in inflammation, and reduce proinflammatory cytokines through the Akt/mTOR/NF-κB axis in c-EAN rats, which could be beneficial for the development of CIDP-related research.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica
/
Neurite Autoimune Experimental
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article