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A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases

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...

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Autores principales: Huertas-Bello, Marcela, Cuéllar-Sáenz, Jerson Andrés, Rodriguez, Cristian Nicolas, Cortés-Vecino, Jesús Alfredo, Navarrete, Myriam Lucia, Avila, Marcel Yecid, Koudouna, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138382/
https://www.ncbi.nlm.nih.gov/pubmed/37108070
http://dx.doi.org/10.3390/ijms24086904
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author Huertas-Bello, Marcela
Cuéllar-Sáenz, Jerson Andrés
Rodriguez, Cristian Nicolas
Cortés-Vecino, Jesús Alfredo
Navarrete, Myriam Lucia
Avila, Marcel Yecid
Koudouna, Elena
author_facet Huertas-Bello, Marcela
Cuéllar-Sáenz, Jerson Andrés
Rodriguez, Cristian Nicolas
Cortés-Vecino, Jesús Alfredo
Navarrete, Myriam Lucia
Avila, Marcel Yecid
Koudouna, Elena
author_sort Huertas-Bello, Marcela
collection PubMed
description 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.
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spelling pubmed-101383822023-04-28 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 Koudouna, Elena Int J Mol Sci Article 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. MDPI 2023-04-07 /pmc/articles/PMC10138382/ /pubmed/37108070 http://dx.doi.org/10.3390/ijms24086904 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huertas-Bello, Marcela
Cuéllar-Sáenz, Jerson Andrés
Rodriguez, Cristian Nicolas
Cortés-Vecino, Jesús Alfredo
Navarrete, Myriam Lucia
Avila, Marcel Yecid
Koudouna, Elena
A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases
title A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases
title_full A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases
title_fullStr A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases
title_full_unstemmed A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases
title_short A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases
title_sort pilot study to evaluate genipin in staphylococcus aureus and pseudomonas aeruginosa keratitis models: modulation of pro-inflammatory cytokines and matrix metalloproteinases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138382/
https://www.ncbi.nlm.nih.gov/pubmed/37108070
http://dx.doi.org/10.3390/ijms24086904
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