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Int. J. Mol. Sci. 2017, 18(3), 562;

Inhibition of NLRP3 Inflammasome Pathway by Butyrate Improves Corneal Wound Healing in Corneal Alkali Burn

Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA
Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Author to whom correspondence should be addressed.
Academic Editor: Allison Cowin
Received: 26 January 2017 / Revised: 27 February 2017 / Accepted: 28 February 2017 / Published: 5 March 2017
(This article belongs to the Special Issue Wound Repair and Regeneration)
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Epithelial cells are involved in the regulation of innate and adaptive immunity in response to different stresses. The purpose of this study was to investigate if alkali-injured corneal epithelia activate innate immunity through the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. A unilateral alkali burn (AB) was created in the central cornea of C57BL/6 mice. Mice received either no topical treatment or topical treatment with sodium butyrate (NaB), β-hydroxybutyric acid (HBA), dexamethasone (Dex), or vehicle (balanced salt solution, BSS) quater in die (QID) for two or five days (d). We evaluated the expression of inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1, as well as the downstream cytokine interleukin (IL)-1β. We found elevation of NLRP3 and IL-1β messenger RNA (mRNA) transcripts, as well as levels of inflammasome component proteins in the alkali-injured corneas compared to naïve corneas. Treatment with NLRP3 inhibitors using NaB and HBA preserved corneal clarity and decreased NLRP3, caspase-1, and IL-1β mRNA transcripts, as well as NLRP3 protein expression on post-injury compared to BSS-treated corneas. These findings identified a novel innate immune signaling pathway activated by AB. Blocking the NLRP3 pathway in AB mouse model decreases inflammation, resulting in greater corneal clarity. These results provide a mechanistic basis for optimizing therapeutic intervention in alkali injured eyes. View Full-Text
Keywords: alkali injury; NLRP3 inflammasome; sodium butyrate; β-hydroxybutyric acid alkali injury; NLRP3 inflammasome; sodium butyrate; β-hydroxybutyric acid

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Bian, F.; Xiao, Y.; Zaheer, M.; Volpe, E.A.; Pflugfelder, S.C.; Li, D.-Q.; de Paiva, C.S. Inhibition of NLRP3 Inflammasome Pathway by Butyrate Improves Corneal Wound Healing in Corneal Alkali Burn. Int. J. Mol. Sci. 2017, 18, 562.

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