Skip Navigation LinksHome > August 2014 - Volume 59 - Issue 2 > Inhibition of p38 Mitogen-Activated Protein Kinase Attenuate...
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0000000000000369
Original Articles: Gastroenterology

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

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

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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.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,


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