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Alfred S Lewin, Chulbul M Ahmed, Howard M Johnson; A Cell Penetrating Peptide from Type I Interferon Protects Mice Against Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):244.
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© ARVO (1962-2015); The Authors (2016-present)
Type I interferons are able to suppress inflammation and have been exploited for treatment of multiple sclerosis, psoriasis and celiac disease, though use of interferon is often associated with severe toxicity. A cell penetrating peptide from the C-terminus of interferon alpha, denoted as IFNα-C, was tested for its ability to suppress inflammatory markers and protect against loss of tight junction proteins in ARPE-19 cells and for its ability to protect against experimental autoimmune uveitis (EAU) in mice.
A peptide from interferon α1, spanning amino acids 152-189, denoted as IFNα-C was conjugated to palmitoyl-lysine for cell penetration. Using real-time quantitative PCR, this peptide showed the induction of anti-inflammatory genes in ARPE-19 cells. The peptide also suppressed the production of inflammatory cytokines and chemokines. The integrity of the RPE cell monolayer was assessed by immunostaining with zona occludin 1 (ZO-1) antibody and by measuring transepithelial electrical resistance (TEER) in cells treated with TNFα in the presence or absence of IFNα-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) to develop EAU and treated with IFNα-C or PBS by daily gavage. The course of disease was monitored by by fundoscopy, SD-OCT, and ERG.
Expression of anti-inflammatory mediators, such as TGFβ, ICAM1, TWST1, TTP, and Foxp3 was induced in ARPE-19 cells treated with IFNα-C. Induction of IL-1β, IL-6, IL-8 and CCL-2 in TNF-α treated cells was attenuated when IFNα-C was simultaneously present. Treatment with TNFα led to a decrease in TEER that was prevented in the presence of IFNα-C peptide. Protection of the integrity of the tight junctions was also documented by ZO-1 staining in cells treated with TNFα in the presence of IFNα-C. Daily treatment with IFNα-C reduced cellular infiltrates and damage to the retina in the mouse EAU model.
Our demonstration that IFNα-C peptide exhibits anti-inflammatory properties and protects against the damage caused in mice with EAU suggests that it has therapeutic potential for the treatment of uveitis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Mice subjected to experimental autoimmune uveitis and treated with interferon alpha C peptide had significantly reduced intravitreal infiltrates compared to control animals treated with phosphate buffered saline.
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