scholarly journals Rebeccamycin Attenuates TNF-α-Induced Intestinal Epithelial Barrier Dysfunction by Inhibiting Myosin Light Chain Kinase Production

2017 ◽  
Vol 41 (5) ◽  
pp. 1924-1934 ◽  
Author(s):  
Akihiro Watari ◽  
Yuta Sakamoto ◽  
Kota Hisaie ◽  
Kazuki Iwamoto ◽  
Miho Fueta ◽  
...  
Keyword(s):  
Barrier Function ◽  
Myosin Light Chain ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Cell Monolayers ◽  
Tnf Α ◽  
Epithelial Barrier Dysfunction

Background/Aims: Although proinflammatory cytokine–induced disruption of intestinal epithelial barrier integrity is associated with intestinal inflammatory disease, effective treatment for barrier dysfunction is lacking. Previously, we demonstrated that rebeccamycin alleviates epithelial barrier dysfunction induced by inflammatory cytokines in Caco-2 cell monolayers; however, the underlying mechanism remained unclear. Here, we investigated the mechanism by which rebeccamycin protects the epithelial barrier function of Caco-2 cells exposed to TNF-α. Methods: To confirm the epithelial barrier function of Caco-2 cell monolayers, transepithelial electrical resistance (TER) and paracellular permeability were measured. Production levels and localization of tight junction (TJ) proteins were analyzed by immunoblot and immunofluorescence, respectively. Phosphorylated myosin light chain (pMLC) and MLC kinase (MLCK) mRNA expression levels were determined by immunoblot and quantitative RT-PCR, respectively. Results: Rebeccamycin attenuated the TNF-α-induced reduction in TER and increase in paracellular permeability. Rebeccamycin increased claudin-5 expression, but not claudin-1, -2, -4, occludin or ZO-1 expression, and prevented the TNF-α-induced changes in ZO-1 and occludin localization. Rebeccamycin suppressed the TNF-α-induced increase in MLCK mRNA expression, thus suppressing MLC phosphorylation. The rebeccamycin-mediated reduction in MLCK production and protection of epithelial barrier function were alleviated by Chk1 inhibition. Conclusion: Rebeccamycin attenuates TNF-α-induced disruption of intestinal epithelial barrier integrity by inducing claudin-5 expression and suppressing MLCK production via Chk1 activation.

scholarly journals Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism

2013 ◽  
Vol 304 (5) ◽  
pp. G479-G489 ◽  
Author(s):  
Katherine R. Groschwitz ◽  
David Wu ◽  
Heather Osterfeld ◽  
Richard Ahrens ◽  
Simon P. Hogan
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Epithelial Barrier Dysfunction

Mast cells regulate intestinal barrier function during disease and homeostasis. Secretion of the mast cell-specific serine protease chymase regulates homeostasis. In the present study, we employ in vitro model systems to delineate the molecular pathways involved in chymase-mediated intestinal epithelial barrier dysfunction. Chymase stimulation of intestinal epithelial (Caco-2 BBe) cell monolayers induced a significant reduction in transepithelial resistance, indicating decreased intestinal epithelial barrier function. The chymase-induced intestinal epithelial barrier dysfunction was characterized by chymase-induced protease-activated receptor (PAR)-2 activation and matrix metalloproteinase (MMP)-2 expression and activation. Consistent with this observation, in vitro analysis revealed chymase-induced PAR-2 activation and increased MAPK activity and MMP-2 expression. Pharmacological and small interfering RNA-mediated antagonism of PAR-2 and MMP-2 significantly attenuated chymase-stimulated barrier dysfunction. Additionally, the chymase/MMP-2-mediated intestinal epithelial dysfunction was associated with a significant reduction in the tight junction protein claudin-5, which was partially restored by MMP-2 inhibition. Finally, incubation of Caco-2 BBe cells with chymase-sufficient, but not chymase-deficient, bone marrow-derived mast cells decreased barrier function, which was attenuated by the chymase inhibitor chymostatin. Collectively, these results suggest that mast cell/chymase-mediated intestinal epithelial barrier function is mediated by PAR-2/MMP-2-dependent pathways.

Polyamines are required for expression of Toll-like receptor 2 modulating intestinal epithelial barrier integrity

2007 ◽  
Vol 293 (3) ◽  
pp. G568-G576 ◽  
Author(s):  
Jie Chen ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
Bernard S. Marasa ◽  
...  
Keyword(s):  
Barrier Function ◽  
Low Dose ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Tlr2 Expression ◽  
Epithelial Barrier Function ◽  
Cell Functions ◽  
Epithelial Barrier Dysfunction

The Toll-like receptors (TLRs) allow mammalian intestinal epithelium to detect various microbes and activate innate immunity after infection. TLR2 and TLR4 have been identified in intestinal epithelial cells (IECs) as fundamental components of the innate immune response to bacterial pathogens, but the exact mechanism involved in control of TLR expression remains unclear. Polyamines are implicated in a wide variety of biological functions, and regulation of cellular polyamines is a central convergence point for the multiple signaling pathways driving different epithelial cell functions. The current study determined whether polyamines regulate TLR expression, thereby modulating intestinal epithelial barrier function. Depletion of cellular polyamines by inhibiting ornithine decarboxylase (ODC) with α-difluoromethylornithine decreased levels of TLR2 mRNA and protein, whereas increased polyamines by ectopic overexpression of the ODC gene enhanced TLR2 expression. Neither intervention changed basal levels of TLR4. Exposure of normal IECs to low-dose (5 μg/ml) LPS increased ODC enzyme activity and stimulated expression of TLR2 but not TLR4, while polyamine depletion prevented this LPS-induced TLR2 expression. Decreased TLR2 in polyamine-deficient cells was associated with epithelial barrier dysfunction. In contrast, increased TLR2 by the low dose of LPS enhanced epithelial barrier function, which was abolished by inhibition of TLR2 expression with specific, small interfering RNA. These results indicate that polyamines are necessary for TLR2 expression and that polyamine-induced TLR2 activation plays an important role in regulating epithelial barrier function.

Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions

2017 ◽  
Vol 8 (3) ◽  
pp. 1144-1151 ◽  
Author(s):  
Qianru Chen ◽  
Oliver Chen ◽  
Isabela M. Martins ◽  
Hu Hou ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Cell Monolayers ◽  
Collagen Peptides ◽  
Epithelial Barrier Dysfunction

Alaska pollock skin derived collagen peptides could be considered as dietary supplements for intestinal barrier function promotion and associated diseases.

Total polysaccharides of adlay bran (Coix lachryma-jobi L.) improve TNF-α induced epithelial barrier dysfunction in Caco-2 cells via inhibition of the inflammatory response

2019 ◽  
Vol 10 (5) ◽  
pp. 2906-2913 ◽  
Author(s):  
Yanlong Li ◽  
Xudong Tian ◽  
Shengcai Li ◽  
Lijun Chang ◽  
Ping Sun ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Irritable Bowel Syndrome ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
Epithelial Barrier Dysfunction

Dysfunction of the intestinal epithelial barrier plays an important role in the pathogenesis of several intestinal diseases, including celiac disease, inflammatory bowel disease, and irritable bowel syndrome.

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