Indole3propionic acid alleviates intestinal epithelial cell injury via regulation of the TLR4/NFκB pathway to improve intestinal barrier function.
Mol Med Rep
; 30(4)2024 10.
Article
em En
| MEDLINE
| ID: mdl-39219265
ABSTRACT
Indole3propionic acid (IPA), a product of Clostridium sporogenes metabolism, has been shown to improve intestinal barrier function. In the present study, in vitro experiments using NCM460 human colonic epithelial cells were performed to investigate how IPA alleviates lipopolysaccharide (LPS)induced intestinal epithelial cell injury, with the aim of improving intestinal barrier function. In addition, the underlying mechanism was explored. NCM460 cell viability and apoptosis were measured using the Cell Counting Kit8 assay and flow cytometry, respectively. The integrity of the intestinal epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER). The underlying molecular mechanism was explored using western blotting, immunofluorescence staining, a dual luciferase reporter gene assay and quantitative PCR. The results showed that 10 µg/ml LPS induced the most prominent decrease in cell viability after 24 h of treatment. By contrast, IPA effectively inhibited LPSinduced apoptosis in the intestinal epithelial cells. Additionally, >0.5 mM IPA improved intestinal barrier function by increasing TEER and upregulating the expression of tight junction proteins (zonula occludens1, claudin1 and occludin). Furthermore, IPA inhibited the release of proinflammatory cytokines (IL1ß, IL6 and TNFα) in a dosedependent manner and this was achieved via regulation of the Tolllike receptor 4 (TLR4)/myeloid differentiation factor 88/NFκB and TLR4/TRIF/NFκB pathways. In conclusion, IPA may alleviate LPSinduced inflammatory injury in human colonic epithelial cells. Taken together, these results suggest that IPA may be a potential therapeutic approach for the management of diseases characterized by LPSinduced intestinal epithelial cell injury and intestinal barrier dysfunction.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Lipopolissacarídeos
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NF-kappa B
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Apoptose
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Células Epiteliais
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Receptor 4 Toll-Like
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Indóis
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Mucosa Intestinal
Limite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Grécia