A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis.
PLoS One
; 15(2): e0227524, 2020.
Article
em En
| MEDLINE
| ID: mdl-32101556
ABSTRACT
Experimental autoimmune uveitis (EAU) in rodents recapitulates many features of the disease in humans and has served as a useful tool for the development of therapeutics. A peptide from C-terminus of interferon α1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFNα-C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFNα-C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNFα were suppressed when IFNα-C was simultaneously present. TNF-α mediated induction of NF-κB and signaling by IL-17A were attenuated by IFNα-C. Differentiated ARPE-19 cells were treated with TNFα in the presence or absence IFNα-C and analyzed by immmunhistochemistry. IFNα-C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNFα was prevented by IFNα-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFNα-C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFNα-C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigen-specific T cell proliferation that was inhibited in the presence of IFNα-C. IFNα-C peptide exhibits anti-inflammatory properties and protects mice against damage to retinal structure and function suggesting that it has therapeutic potential for the treatment of autoimmune uveitis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Retina
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Doenças Autoimunes
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Uveíte
/
Interferon Tipo I
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article