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Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation. | LitMetric

Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation.

iScience

Department of Ophthalmology and Visual Sciences, University of Illinois Medical Center, 1855 W. Taylor Street, MC 648, Chicago, IL 60612, USA.

Published: December 2022

AI Article Synopsis

Article Abstract

Chronic inflammation of the immune privileged cornea originating from viral or nonviral conditions results in significant vision loss. Topical corticosteroids are the common treatments for corneal inflammation, but the drugs cause serious and potentially blinding side effects in the long term. Therefore, new standalone and/or synergistic anti-inflammatory therapies with lower side effects are desperately needed. Here, we show that the aromatic fatty acid phenylbutyrate (PBA) acts as a potent inhibitor of inflammation in preclinical ocular-inflammation models. PBA prevents the transcription as well as translation of pro-inflammatory cytokines by LPS and poly(I:C) via persistent inhibition of NF-κB signaling. PBA quickens the resolution of ocular inflammation in mice by decreasing corneal thickness and immune cell infiltration. More importantly, PBA can synergize with the dexamethasone to antagonize NF-κB signaling at lower drug concentrations. Our results demonstrate that PBA therapy exerts previously unreported anti-inflammatory effects in the eye and facilitates corneal healing during persistent inflammation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9758524PMC
http://dx.doi.org/10.1016/j.isci.2022.105682DOI Listing

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