title: Inhibition of p38 mitogen-activated protein kinase attenuates butyrate-induced intestinal barrier impairment in a Caco-2 cell monolayer model.
abstract: OBJECTIVE
  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.
authors.affiliation: *Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China †Department of Critical Care Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China ‡Kravis Children's Hospital of the Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Huang
authors.forename: Zhong-Rong
authors.initials: ZR
authors.lastname: Li
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Zhu
authors.forename: Hui-Ya
authors.initials: HY
authors.lastname: Huang
authors.forename: Long-Long
authors.initials: LL
authors.lastname: Hou
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000009:adverse effects*; D018938:Caco-2 Cells; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D007410:Intestinal Diseases / Q000201:enzymology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism; D007444:Inulin / Q000378:metabolism; D010539:Permeability; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D002087:Butyrates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D007444:Inulin; D048051:p38 Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate; C093642:SB 203580