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Inhibition of p38 Mitogen-Activated Protein Kinase Attenuates Butyrate-Induced Intestinal Barrier Impairment in a Caco-2 Cell Monolayer Model

Inhibition of p38 Mitogen-Activated Protein Kinase Attenuates Butyrate-Induced Intestinal Barrier Impairment in a Caco-2 Cell Monolayer Model

Xiao-Zhong Huang, Zhong-Rong Li, Li-Bin Zhu, Hui-Ya Huang, Long-Long Hou, Jing Lin

J Pediatr Gastroenterol Nutr. 2014 Aug;59(2):264-9.

PMID: 24625969

Abstract:

Objectives:
Butyrate is well known to induce apoptosis in differentiating intestinal epithelial cells. The present study was designed to examine the role of p38 mitogen-activated protein kinase (MAPK) in butyrate-induced intestinal barrier impairment.
Methods:
The intestinal barrier was determined by measuring the transepithelial electrical resistance (TER) in a Caco-2 cell monolayer model. The permeability was determined by measuring transepithelial passage of fluorescein isothiocyanate-conjugated inulin (inulin-FITC). The morphology of the monolayers was examined with scanning electron microscopy. The apoptosis status was determined by annexin V-FITC labeling and flow cytometry. The activity of p38 MAPK was determined by the phosphorylation status of p38 with Western blotting.
Results:
Butyrate at 5 mM increases the apoptosis rate of Caco-2 cells and induces impairment of intestinal barrier functions as determined by decreased TER and increased inulin-FITC permeability. Butyrate treatment activates p38 MAPK in a concentration- and time-dependent manner. SB203580, a specific p38 inhibitor, inhibits butyrate-induced Caco-2 cell apoptosis. Treatment of SB203580 significantly attenuates the butyrate-induced impairment of barrier functions in the Caco-2 cell monolayer model.
Conclusions:
p38 MAPK can be activated by butyrate and is involved in the butyrate-induced apoptosis and impairment of intestinal barrier function. Inhibition of p38 MAPK can significantly attenuate butyrate-induced intestinal barrier dysfunction.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR424675	Inulin-FITC			Price

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