title: Somatostatin ameliorates lipopolysaccharide-induced tight junction damage via the ERK-MAPK pathway in Caco2 cells.
abstract: Dysfunction of the epithelial barrier is an important pathogenic factor of inflammatory bowel disease and other inflammatory conditions of the gut. Somatostatin (SST) has been demonstrated to reduce local and systemic inflammation reactions and maintain the integrity of the blood-brain barrier (BBB). To determine the beneficial effect of SST on lipopolysaccharide (LPS)-induced damage of the tight junction (TJ) and its mechanisms, Caco2 cells pretreated with SST (1nM) or MEK inhibitor U0126 (10μM) were exposed to LPS. LPS significantly reduced the expression of TJ proteins in a dose-dependent way. LPS (100μg/ml) greatly induced Caco2 monolayer barrier dysfunction by decreasing transepithelial resistance and increasing epithelial permeability. Pretreatment with SST effectively improved the barrier dysfunction of Caco2 cells. SST significantly increased the expression of TJ proteins occludin and ZO-1 and inhibited the redistribution of TJ proteins due to LPS stimulation. Furthermore, SST decreased the LPS-induced phosphorylation of ERK1/2, and a selective MEK inhibitor markedly protected the barrier function against LPS disturbance by blocking the activation of the ERK-MAPK pathway in Caco2 cells. Besides, LPS significantly increased the mRNA level of SSTR5, which was partly inhibited by pretreatment with SST. In conclusion, the present study indicates that SST protects the Caco2 monolayer barrier against LPS-induced tight junction breakdown by down-regulating the activation of the ERK-MAPK pathway and suppression the activation of SSTR5.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lei
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Wendi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: zhifc41532@163.com.
authors.forename: Fachao
authors.initials: F
authors.lastname: Zhi
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D002070:Butadienes; D008070:Lipopolysaccharides; D009570:Nitriles; D062793:Occludin; D017481:Receptors, Somatostatin; C113580:U 0126; D062826:Zonula Occludens-1 Protein; D013004:Somatostatin; C094573:somatostatin receptor 5; D020928:Mitogen-Activated Protein Kinases
keywords: ERK–MAPK pathway; Lipopolysaccharide; Permeability; Somatostatin; Tight junction