We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Protective Effects of Carbon Monoxide-Releasing Molecule-2 on the Barrier Function of Intestinal Epithelial Cells.
- Authors
Mu, Xinwei; Pan, Chen; Zheng, Shuyun; Alhamdi, Yasir; Sun, Bingwei; Shi, Qiankun; Wang, Xiang; Sun, Zhiwei; Toh, Chenghock; Wang, Guozheng
- Abstract
Objective: To investigate the protective effects and mechanisms of carbon monoxide-releasing molecule-2 (CORM-2) on barrier function of intestinal epithelial cells. Materials and Methods: After pre-incubation with CORM-2 for 1 hour, cultured intestinal epithelial IEC-6 cells were stimulated with 50 µg/ml lipopolysaccharides (LPS). Cytokines levels in culture medium were detected using ELISA kits. Trans-epithelial electrical resistance (TER) of IEC-6 cell monolayers in Transwells were measured with a Millipore electric resistance system (ERS-2; Millipore) and calculated as Ω/cm2 at different time points after LPS treatment. The permeability changes were also measured using FITC-dextran. The levels of tight junction (TJ) proteins (occludin and ZO-1) and myosin light chain (MLC) phosphorylation were detected using Western blotting with specific antibodies. The subsequent structural changes of TJ were visualized using transmission electron microscopy (TEM). Results: CORM-2 significantly reduced LPS-induced secretion of TNF-α and IL-1β. The LPS-induced decrease of TER and increase of permeability to FITC-dextran were inhibited by CORM-2 in a concentration dependent manner (P<0.05). LPS-induced reduction of tight junction proteins and increase of MLC phosphorylation were also attenuated. In LPS-treated cells, TEM showed diminished electron-dense material and interruption of TJ and desmosomes between the apical lateral margins of adjoining cells, which were prevented by CORM-2 treatment. Conclusions: The present study demonstrates that CORM-2, as a novel CO-releasing molecule, has ability to protect the barrier function of LPS-stimulated intestinal epithelial cells. Inhibition of inflammatory cytokines release, restoration of TJ proteins and suppression of MLC phosphorylation are among the protective effects of CORM-2.
- Subjects
PHYSIOLOGICAL effects of carbon monoxide; INTESTINAL physiology; EPITHELIAL cells; LIPOPOLYSACCHARIDES; ELECTRIC resistance; CRITICAL care medicine; EMERGENCY medicine
- Publication
PLoS ONE, 2014, Vol 9, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0104032