A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis.
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 fo...
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doaj-5f8efb8f84334029a4393ec3c14d0c802021-03-03T21:27:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01152e022752410.1371/journal.pone.0227524A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis.Chulbul M AhmedCristhian J IldefonsoHoward M JohnsonAlfred S LewinExperimental 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.https://doi.org/10.1371/journal.pone.0227524 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chulbul M Ahmed Cristhian J Ildefonso Howard M Johnson Alfred S Lewin |
spellingShingle |
Chulbul M Ahmed Cristhian J Ildefonso Howard M Johnson Alfred S Lewin A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis. PLoS ONE |
author_facet |
Chulbul M Ahmed Cristhian J Ildefonso Howard M Johnson Alfred S Lewin |
author_sort |
Chulbul M Ahmed |
title |
A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis. |
title_short |
A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis. |
title_full |
A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis. |
title_fullStr |
A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis. |
title_full_unstemmed |
A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis. |
title_sort |
c-terminal peptide from type i interferon protects the retina in a mouse model of autoimmune uveitis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0227524 |
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