A pilot study to evaluate genipin in staphylococcus aureus and pseudomonas aeruginosa keratitis models: Modulation of pro-inflammatory cytokines and matrix metalloproteinases

Huertas-Bello, Marcela, Cuéllar-Sáenz, Jerson Andrés, Rodriguez, Cristian Nicolas, Cortés-Vecino, Jesús Alfredo, Navarrete, Myriam Lucia, Avila, Marcel Yecid and Koudouna, Elena ORCID: https://orcid.org/0000-0002-9959-4667 2023. A pilot study to evaluate genipin in staphylococcus aureus and pseudomonas aeruginosa keratitis models: Modulation of pro-inflammatory cytokines and matrix metalloproteinases. International Journal of Molecular Sciences 24 (8) , 6904. 10.3390/ijms24086904

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Abstract

Infectious keratitis is a vision-threatening microbial infection. The increasing antimicrobial resistance and the fact that severe cases often evolve into corneal perforation necessitate the development of alternative therapeutics for effective medical management. Genipin, a natural crosslinker, was recently shown to exert antimicrobial effects in an ex vivo model of microbial keratitis, highlighting its potential to serve as a novel treatment for infectious keratitis. This study aimed to evaluate the antimicrobial and anti-inflammatory effects of genipin in an in vivo model of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) keratitis. Clinical scores, confocal microscopy, plate count, and histology were carried out to evaluate the severity of keratitis. To assess the effect of genipin on inflammation, the gene expression of pro- and anti-inflammatory factors, including matrix metalloproteinases (MMPs), were evaluated. Genipin treatment alleviated the severity of bacterial keratitis by reducing bacterial load and repressing neutrophil infiltration. The expression of interleukin 1B (IL1B), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 15 (IL15), tumor necrosis factor-α (TNF-α), and interferon γ (IFNγ), as well as MMP2 and MMP9, were significantly reduced in genipin-treated corneas. Genipin promoted corneal proteolysis and host resistance to S. aureus and P. aeruginosa infection by suppressing inflammatory cell infiltration, regulating inflammatory mediators, and downregulating the expression of MMP2 and MMP9.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Optometry and Vision Sciences
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	MDPI
ISSN:	1422-0067
Date of First Compliant Deposit:	9 May 2023
Date of Acceptance:	1 April 2023
Last Modified:	05 Jan 2024 05:45
URI:	https://orca.cardiff.ac.uk/id/eprint/159322

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