Mechanism of IL-1β-Induced Increase in Intestinal Epithelial Tight Junction Permeability
- 15 April 2008
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 180 (8), 5653-5661
- https://doi.org/10.4049/jimmunol.180.8.5653
Abstract
The IL-1β-induced increase in intestinal epithelial tight junction (TJ) permeability has been postulated to be an important mechanism contributing to intestinal inflammation of Crohn’s disease and other inflammatory conditions of the gut. The intracellular and molecular mechanisms that mediate the IL-1β-induced increase in intestinal TJ permeability remain unclear. The purpose of this study was to elucidate the mechanisms that mediate the IL-1β-induced increase in intestinal TJ permeability. Specifically, the role of myosin L chain kinase (MLCK) was investigated. IL-1β caused a progressive increase in MLCK protein expression. The time course of IL-1β-induced increase in MLCK level correlated linearly with increase in Caco-2 TJ permeability. Inhibition of the IL-1β-induced increase in MLCK protein expression prevented the increase in Caco-2 TJ permeability. Inhibition of the IL-1β-induced increase in MLCK activity also prevented the increase in Caco-2 TJ permeability. Additionally, knock-down of MLCK protein expression by small interference RNA prevented the IL-1β-induced increase in Caco-2 TJ permeability. The IL-1β-induced increase in MLCK protein expression was preceded by an increase in MLCK mRNA expression. The IL-1β-induced increase in MLCK mRNA transcription and subsequent increase in MLCK protein expression and Caco-2 TJ permeability was mediated by activation of NF-κB. In conclusion, our data indicate that the IL-1β increase in Caco-2 TJ permeability was mediated by an increase in MLCK expression and activity. Our findings also indicate that the IL-1β-induced increase in MLCK protein expression and Caco-2 TJ permeability was mediated by an NF-κB-dependent increase in MLCK gene transcription.Keywords
This publication has 74 references indexed in Scilit:
- The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disordersClinical and Experimental Immunology, 2007
- Inflammatory bowel disease: is it really just another break in the wall?Gut, 2007
- Disruption of Tight Junctions and Induction of Proinflammatory Cytokine Responses in Colonic Epithelial Cells by Campylobacter jejuniInfection and Immunity, 2006
- IFN-γ-Induced TNFR2 Expression Is Required for TNF-Dependent Intestinal Epithelial Barrier DysfunctionGastroenterology, 2006
- Mechanism of IFN-γ-induced Endocytosis of Tight Junction Proteins: Myosin II-dependent Vacuolarization of the Apical Plasma MembraneMolecular Biology of the Cell, 2005
- Effects of the Chemokine CCL2 on Blood–Brain Barrier Permeability during Ischemia–Reperfusion InjuryJournal of Cerebral Blood Flow & Metabolism, 2005
- Effect of proinflammatory interleukins on jejunal nutrient transportGut, 2000
- Cyclic GMP-Dependent Stimulation Reverses G-Protein-Coupled Inhibition of Smooth Muscle Myosin Light Chain PhosphataseBiochemical and Biophysical Research Communications, 1996
- Cytokine production in patients with inflammatory bowel disease.Gut, 1992
- Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers.JCI Insight, 1988