| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print December 4, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00309.2002
Submitted on July 2, 2002
Accepted on November 27, 2002
1 Pediatrics, Vanderbilt University, Nashville, TN, USA
2 Medicine, Vanderbilt University, Nashville, TN, USA; Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
3 Pediatrics, Vanderbilt University, Nashville, TN, USA; Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: d-brent.polk{at}vanderbilt.edu.
Altered mucosal integrity and increased cytokine production, including tumor necrosis factor (TNF) are the hallmarks of inflammatory bowel disease (IBD). In this study, we addressed the role of TNF receptors (TNFR) on intestinal epithelial cell migration in an in vitro wound closure model. Using mouse TNFR1 or TNFR2 knock-out intestinal epithelial cells, gene transfection, and pharmacological inhibitors, we show a concentration-dependent receptor-mediated regulation of intestinal cell migration by TNF. Physiological TNF level (1 ng/ml) enhances migration through TNFR2 whereas pathological level (100 ng/ml) inhibits wound closure through TNFR1. Increased rate of wound closure by TNFR2 or inhibition by TNFR1 cannot be explained by either increased proliferation or apoptosis, respectively. Furthermore, inhibiting Src tyrosine kinase decreases TNF-induced focal adhesion kinase (FAK) tyrosine phosphorylation and cellular migration. We therefore conclude that TNFR2 activates a novel Src-regulated pathway involving FAK tyrosine phosphorylation that enhances migration of intestinal epithelial cells.
This article has been cited by other articles:
|
|
 |
|
  R. Palumbo, F. De Marchis, T. Pusterla, A. Conti, M. Alessio, and M. E. Bianchi Src family kinases are necessary for cell migration induced by extracellular HMGB1 J. Leukoc. Biol., September 1, 2009; 86(3): 617 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Mathew, D. Haubert, M. Kronke, and M. Leptin Looking beyond death: a morphogenetic role for the TNF signalling pathway J. Cell Sci., June 15, 2009; 122(12): 1939 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. McElroy, M. R. Frey, F. Yan, K. L. Edelblum, J. A. Goettel, S. John, and D. B. Polk Tumor necrosis factor inhibits ligand-stimulated EGF receptor activation through a TNF receptor 1-dependent mechanism Am J Physiol Gastrointest Liver Physiol, August 1, 2008; 295(2): G285 - G293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Dise, M. R. Frey, R. H. Whitehead, and D. B. Polk Epidermal growth factor stimulates Rac activation through Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migration Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G276 - G285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Willing and A. G. Van Kessel Enterocyte proliferation and apoptosis in the caudal small intestine is influenced by the composition of colonizing commensal bacteria in the neonatal gnotobiotic pig J Anim Sci, December 1, 2007; 85(12): 3256 - 3266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Shirkey, R. H. Siggers, B. G. Goldade, J. K. Marshall, M. D. Drew, B. Laarveld, and A. G. Van Kessel Effects of Commensal Bacteria on Intestinal Morphology and Expression of Proinflammatory Cytokines in the Gnotobiotic Pig Experimental Biology and Medicine, September 1, 2006; 231(8): 1333 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gunzel, P. Florian, J. F. Richter, H. Troeger, J. D. Schulzke, M. Fromm, and A. H. Gitter Restitution of single-cell defects in the mouse colon epithelium differs from that of cultured cells Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2006; 290(6): R1496 - R1507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Fenton and N. G. Hord Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research Carcinogenesis, May 1, 2006; 27(5): 893 - 902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Tong, E. V. Vassilieva, A. I. Ivanov, Z. Wang, G. T. Brown, C. A. Parkos, and A. Nusrat Interferon-{gamma} Inhibits T84 Epithelial Cell Migration by Redirecting Transcytosis of {beta}1 Integrin from the Migrating Leading Edge J. Immunol., September 15, 2005; 175(6): 4030 - 4038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Myhre, M. Toruner, S. Abraham, and L. J. Egan Metalloprotease disintegrin-mediated ectodomain shedding of EGFR ligands promotes intestinal epithelial restitution Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1213 - G1219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Sanders and M. D. Basson Collagen IV regulates Caco-2 migration and ERK activation via {alpha}1{beta}1- and {alpha}2{beta}1-integrin-dependent Src kinase activation Am J Physiol Gastrointest Liver Physiol, April 1, 2004; 286(4): G547 - G557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Funakoshi-Tago, Y. Sonoda, S. Tanaka, K. Hashimoto, K. Tago, S.-i. Tominaga, and T. Kasahara Tumor Necrosis Factor-induced Nuclear Factor {kappa}B Activation Is Impaired in Focal Adhesion Kinase-deficient Fibroblasts J. Biol. Chem., August 1, 2003; 278(31): 29359 - 29365. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
