| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
and Tumor Necrosis Factor-
Synergize to Induce Intestinal Epithelial Barrier Dysfunction by Up-Regulating Myosin Light Chain Kinase Expression
From the Institute of Burn Research,* Southwest Hospital, Third Military Medical University, Chongqing, China; and the Department of Pathology, The University of Chicago, Chicago Illinois
Numerous intestinal diseases are characterized by immune cell activation and compromised epithelial barrier function. We have shown that cytokine treatment of epithelial monolayers increases myosin II regulatory light chain (MLC) phosphorylation and decreases barrier function and that these are both reversed by MLC kinase (MLCK) inhibition. The aim of this study was to determine the mechanisms by which interferon (IFN)-
and tumor necrosis factor (TNF)-
regulate MLC phosphorylation and disrupt epithelial barrier function. We developed a model in which both cytokines were required for barrier dysfunction. Barrier dysfunction was also induced by TNF- addition to IFN--primed, but not control, Caco-2 monolayers. TNF- treatment of IFN--primed monolayers caused increases in both MLCK expression and MLC phosphorylation, suggesting that MLCK is a TNF--inducible protein. These effects of TNF- were not mediated by nuclear factor-
B. However, at doses below those needed for nuclear factor-B inhibition, sulfasalazine was able to prevent TNF--induced barrier dysfunction, MLCK up-regulation, and MLC phosphorylation. Low-dose sulfasalazine also prevented morphologically evident tight junction disruption induced by TNF-. These data show that IFN- can prime intestinal epithelial monolayers to respond to TNF- by disrupting tight junction morphology and barrier function via MLCK up-regulation and MLC phosphorylation. These TNF--induced events can be prevented by the clinically relevant drug sulfasalazine.
This article has been cited by other articles:
 |
|
 |
|
  E. Kakiashvili, P. Speight, F. Waheed, R. Seth, M. Lodyga, S. Tanimura, M. Kohno, O. D. Rotstein, A. Kapus, and K. Szaszi GEF-H1 Mediates Tumor Necrosis Factor-{alpha}-induced Rho Activation and Myosin Phosphorylation: ROLE IN THE REGULATION OF TUBULAR PARACELLULAR PERMEABILITY J. Biol. Chem., April 24, 2009; 284(17): 11454 - 11466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Clark, A. Hope, M. Lopez-Fraga, N. Schiller, and D. D. Lo Bacterial Particle Endocytosis by Epithelial Cells Is Selective and Enhanced by Tumor Necrosis Factor Receptor Ligands Clin. Vaccine Immunol., March 1, 2009; 16(3): 397 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kimura, S. Teranishi, and T. Nishida Interleukin-1{beta}-Induced Disruption of Barrier Function in Cultured Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 597 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chichlowski and L. P. Hale Bacterial-mucosal interactions in inflammatory bowel disease--an alliance gone bad Am J Physiol Gastrointest Liver Physiol, December 1, 2008; 295(6): G1139 - G1149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fasano Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation: Living Life on the Edge of the Wall Am. J. Pathol., November 1, 2008; 173(5): 1243 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, L. Xiao, J. N. Rao, T. Zou, L. Liu, E. Bellavance, M. Gorospe, and J.-Y. Wang JunD Represses Transcription and Translation of the Tight Junction Protein Zona Occludens-1 Modulating Intestinal Epithelial Barrier Function Mol. Biol. Cell, September 1, 2008; 19(9): 3701 - 3712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Al-Sadi, D. Ye, K. Dokladny, and T. Y. Ma Mechanism of IL-1{beta}-Induced Increase in Intestinal Epithelial Tight Junction Permeability J. Immunol., April 15, 2008; 180(8): 5653 - 5661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Fries, C. Muja, C. Crisafulli, S. Cuzzocrea, and E. Mazzon Dynamics of enterocyte tight junctions: effect of experimental colitis and two different anti-TNF strategies Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G938 - G947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kimura, S. Teranishi, K. Fukuda, K. Kawamoto, and T. Nishida Delayed Disruption of Barrier Function in Cultured Human Corneal Epithelial Cells Induced by Tumor Necrosis Factor-{alpha} in a Manner Dependent on NF-{kappa}B Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 565 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. B. Bergstrom, J. A. Guttman, M. Rumi, C. Ma, S. Bouzari, M. A. Khan, D. L. Gibson, A. W. Vogl, and B. A. Vallance Modulation of Intestinal Goblet Cell Function during Infection by an Attaching and Effacing Bacterial Pathogen Infect. Immun., February 1, 2008; 76(2): 796 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zeni, E. Doepker, U. S. Topphoff, S. Huewel, T. Tenenbaum, and H.-J. Galla MMPs contribute to TNF-{alpha}-induced alteration of the blood-cerebrospinal fluid barrier in vitro Am J Physiol Cell Physiol, September 1, 2007; 293(3): C855 - C864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sheth, N. Delos Santos, A. Seth, N. F. LaRusso, and R. K. Rao Lipopolysaccharide disrupts tight junctions in cholangiocyte monolayers by a c-Src-, TLR4-, and LBP-dependent mechanism Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G308 - G318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Blikslager, A. J. Moeser, J. L. Gookin, S. L. Jones, and J. Odle Restoration of Barrier Function in Injured Intestinal Mucosa Physiol Rev, April 1, 2007; 87(2): 545 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Al-Sadi and T. Y. Ma IL-1beta Causes an Increase in Intestinal Epithelial Tight Junction Permeability J. Immunol., April 1, 2007; 178(7): 4641 - 4649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. McKay, J. L. Watson, A. Wang, J. Caldwell, D. Prescott, P. M. J. Ceponis, V. Di Leo, and J. Lu Phosphatidylinositol 3'-Kinase Is a Critical Mediator of Interferon-{gamma}-Induced Increases in Enteric Epithelial Permeability J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1013 - 1022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Boivin, D. Ye, J. C. Kennedy, R. Al-Sadi, C. Shepela, and T. Y. Ma Mechanism of glucocorticoid regulation of the intestinal tight junction barrier Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G590 - G598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C R Weber and J R Turner Inflammatory bowel disease: is it really just another break in the wall? Gut, January 1, 2007; 56(1): 6 - 8. [Full Text] [PDF]
|
|
|
|
|
|
C. D'hondt, R. Ponsaerts, S. P. Srinivas, J. Vereecke, and B. Himpens Thrombin Inhibits Intercellular Calcium Wave Propagation in Corneal Endothelial Cells by Modulation of Hemichannels and Gap Junctions Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 120 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Turner Molecular Basis of Epithelial Barrier Regulation: From Basic Mechanisms to Clinical Application Am. J. Pathol., December 1, 2006; 169(6): 1901 - 1909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. deSchoolmeester, H. Manku, and K. J. Else The Innate Immune Responses of Colonic Epithelial Cells to Trichuris muris Are Similar in Mouse Strains That Develop a Type 1 or Type 2 Adaptive Immune Response. Infect. Immun., November 1, 2006; 74(11): 6280 - 6286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Md. R. Amin, J. Malakooti, R. Sandoval, P. K. Dudeja, and K. Ramaswamy IFN-{gamma} and TNF-{alpha} regulate human NHE3 gene expression by modulating the Sp family transcription factors in human intestinal epithelial cell line C2BBe1 Am J Physiol Cell Physiol, November 1, 2006; 291(5): C887 - C896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Herring, O. El-Mounayri, P. J. Gallagher, F. Yin, and J. Zhou Regulation of myosin light chain kinase and telokin expression in smooth muscle tissues Am J Physiol Cell Physiol, November 1, 2006; 291(5): C817 - C827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. V. Graham, F. Wang, D. R. Clayburgh, J. X. Cheng, B. Yoon, Y. Wang, A. Lin, and J. R. Turner Tumor Necrosis Factor-induced Long Myosin Light Chain Kinase Transcription Is Regulated by Differentiation-dependent Signaling Events: CHARACTERIZATION OF THE HUMAN LONG MYOSIN LIGHT CHAIN KINASE PROMOTER J. Biol. Chem., September 8, 2006; 281(36): 26205 - 26215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Shen, E. D. Black, E. D. Witkowski, W. I. Lencer, V. Guerriero, E. E. Schneeberger, and J. R. Turner Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure J. Cell Sci., May 15, 2006; 119(10): 2095 - 2106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Shen and J. R. Turner Role of Epithelial Cells in Initiation and Propagation of Intestinal Inflammation. Eliminating the static: tight junction dynamics exposed Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G577 - G582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Chiba, T. Kojima, M. Osanai, and N. Sawada The Significance of Interferon-{gamma}-Triggered Internalization of Tight-Junction Proteins in Inflammatory Bowel Disease Sci. Signal., January 3, 2006; 2006(316): pe1 - pe1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Buret How Stress Induces Intestinal Hypersensitivity Am. J. Pathol., January 1, 2006; 168(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
|
|
R. Moriez, C. Salvador-Cartier, V. Theodorou, J. Fioramonti, H. Eutamene, and L. Bueno Myosin Light Chain Kinase Is Involved in Lipopolysaccharide-Induced Disruption of Colonic Epithelial Barrier and Bacterial Translocation in Rats Am. J. Pathol., October 1, 2005; 167(4): 1071 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Shen and J. R. Turner Actin Depolymerization Disrupts Tight Junctions via Caveolae-mediated Endocytosis Mol. Biol. Cell, September 1, 2005; 16(9): 3919 - 3936. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
