HucMSC-Ex carrying miR-203a-3p.2 ameliorates colitis through the suppression of caspase11/4-induced macrophage pyroptosis.
Int Immunopharmacol
; 110: 108925, 2022 Sep.
Article
en En
| MEDLINE
| ID: mdl-35724605
ABSTRACT
BACKGROUND:
Inflammatory bowel disease (IBD) is a kind of chronic, idiopathic, and recurrent inflammation, associated with dysregulated intestinal mucosal immunity. Caspase (casp) 11/4-induced macrophage pyroptosis contributes to the development of inflammation, while human umbilical cord mesenchymal stem cell-secreted exosomes (hucMSC-Ex) play a reparative role in IBD.OBJECTIVE:
The present study focused on the treatment of IBD with hucMSC-Ex and its regulatory mechanism via the casp11/4 pathway.METHODS:
BALB/c mice were used to establish a dextran sulfate sodium (DSS)-induced colitis model, and hucMSC-Ex was administered intravenously to estimate its therapeutic effect. In vitro, RAW264.7 cells line, THP-1 cells line, and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) to activate an inflammatory environment of pyroptosis, followed by repairing with hucMSC-Ex. MicroRNA mimics and inhibitors were provided to verify the role of miR-203a-3p.2 from hucMSC-Ex in inflammation. The results were analyzed by Western blot, RT-qPCRãELISA, and LDH secretion.RESULTS:
HucMSC-Ex inhibited the activation of casp11 and reduced the secretion of interleukin (IL)-1ß, IL-6, and casp11, which relieved macrophage pyroptosis to alleviate murine colitis. A consistent outcome was revealed in the cell experiments, where hucMSC-Ex contributed to a decreased casp11/4 expression, and lactate dehydrogenase (LDH) release, as a marker of cell damage. Moreover, miR-203a-3p.2 from hucMSC-Ex functioned as an effective mediator in the interaction with casp4 in THP-1 macrophage pyroptosis.CONCLUSION:
HucMSC-Ex ameliorates colitis through the suppression of casp11/4-induced macrophage pyroptosis, and hucMSC-Ex carrying miR-203a-3p.2 inhibits casp4-induced macrophage pyroptosis in an inflammatory environment.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Inflamatorias del Intestino
/
Colitis
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MicroARNs
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Células Madre Mesenquimatosas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2022
Tipo del documento:
Article