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MicroRNA miR-27a-5p reduces intestinal inflammation induced by Clostridioides difficile flagella by regulating the NF-κB signaling pathway.
Kobeissy, Philippe Hussein; Denève-Larrazet, Cécile; Marvaud, Jean-Christophe; Kansau, Imad.
Afiliación
  • Kobeissy PH; Institut MICALIS (UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech), Equipe Bactéries Pathogènes et Santé, Faculté de Pharmacie, Université Paris-Saclay, 91400 Orsay, France.
  • Denève-Larrazet C; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut 1102-2801, Lebanon.
  • Marvaud JC; Institut MICALIS (UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech), Equipe Bactéries Pathogènes et Santé, Faculté de Pharmacie, Université Paris-Saclay, 91400 Orsay, France.
  • Kansau I; Institut MICALIS (UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech), Equipe Bactéries Pathogènes et Santé, Faculté de Pharmacie, Université Paris-Saclay, 91400 Orsay, France.
J Infect Dis ; 2024 Aug 10.
Article en En | MEDLINE | ID: mdl-39126324
ABSTRACT

BACKGROUND:

Clostridioides difficile is a major cause of nosocomial post-antibiotic infections, often resulting in severe inflammation and watery diarrhea. Previous studies have highlighted the role of C. difficile flagellin FliC in activating the TLR5 receptor and triggering NF-κB cell signaling, leading to the release of pro-inflammatory cytokines. However, the microRNAs (miRNAs) mediated regulatory mechanisms underlying the FliC-induced inflammatory response remain unclear.

METHODS:

miRNA expression levels were analyzed in Caco-2 intestinal epithelial cells following FliC stimulation, infection with the epidemic C. difficile R20291 strain, or its unflagellated mutant by RT-qPCR. Chemical inhibitors were used to block NF-κB signaling, and their impact on miR-27a-5p expression was assessed. Knockdown and overexpression experiments with miRNA inhibitor and mimic were conducted to elucidate miR-27a-5p's functional role in FliC-induced inflammatory responses. Additionally, a mouse model of C. difficile infection was treated with miR-27a-5p to evaluate its therapeutic potential in vivo.

RESULTS:

miR-27a-5p showed significant FliC-dependent overexpression in Caco-2 cells. Inhibition of NF-κB signaling suppressed miR-27a-5p overexpression. Knockdown of miR-27a-5p increased NF-κB activation and TNF-α and IL-8 cytokine production, while its overexpression had the opposite effect. Moreover, miR-27a-5p was overexpressed in the caeca of C. difficile-infected mice, correlating with intestinal IL-8 levels. Treatment of infected mice with miR-27a-5p mimic reduced disease severity and intestinal inflammation.

CONCLUSION:

miR-27a-5p plays a crucial role in regulating C. difficile-induced inflammation, suggesting its potential as a therapeutic target for controlling severe infection. These findings offer valuable insights into potential therapeutic strategies for managing C. difficile infection and associated inflammatory complications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos