AJP - GI AJP: Gastrointestinal and Liver Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 284: G703-G712, 2003. First published December 27, 2002; doi:10.1152/ajpgi.00214.2002
0193-1857/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/4/G703    most recent
00214.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yoo, J.
Right arrow Articles by Matthews, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yoo, J.
Right arrow Articles by Matthews, J. B.
Vol. 284, Issue 4, G703-G712, April 2003

Bryostatin-1 attenuates TNF-induced epithelial barrier dysfunction: role of novel PKC isozymes

James Yoo1, Anthony Nichols2, Jaekyung C. Song2, Joshua Mammen2, Isabel Calvo2, Roger T. Worrell2, John Cuppoletti2, Karl Matlin2, and Jeffrey B. Matthews2

1 Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; and 2 Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio 45267

Tumor necrosis factor (TNF) increases epithelial permeability in many model systems. Protein kinase C (PKC) isozymes regulate epithelial barrier function and alter ligand-receptor interactions. We sought to define the impact of PKC on TNF-induced barrier dysfunction in T84 intestinal epithelia. TNF induced a dose- and time-dependent fall in transepithelial electrical resistance (TER) and an increase in [3H]mannitol flux. The TNF-induced fall in TER was not PKC mediated but was prevented by pretreatment with bryostatin-1, a PKC agonist. As demonstrated by a pattern of sensitivity to pharmacological inhibitors of PKC, this epithelial barrier preservation was mediated by novel PKC isozymes. Bryostatin-1 reduced TNF receptor (TNF-R1) surface availability, as demonstrated by radiolabeled TNF binding and cell surface biotinylation assays, and increased TNF-R1 receptor shedding. The pattern of sensitivity to isozyme-selective PKC inhibitors suggested that these effects were mediated by activation of PKC-epsilon . In addition, after bryostatin-1 treatment, PKC-delta and TNF-R1 became associated, as determined by mutual coimmunoprecipitation assay, which has been shown to lead to receptor desensitization in neutrophils. TNF-induced barrier dysfunction occurs independently of PKC, but selective modulation of novel PKC isozymes may regulate TNF-R1 signaling.

protein kinase C; tumor necrosis factor; epithelial barrier function


This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. R. Wilson, M. E. Goddard, K. P. O'Dea, S. Choudhury, and M. Takata
Differential roles of p55 and p75 tumor necrosis factor receptors on stretch-induced pulmonary edema in mice
Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L60 - L68.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. Banan, L.J. Zhang, M. Shaikh, J.Z. Fields, A. Farhadi, and A. Keshavarzian
{theta}-Isoform of PKC is required for alterations in cytoskeletal dynamics and barrier permeability in intestinal epithelium: a novel function for PKC-{theta}
Am J Physiol Cell Physiol, July 1, 2004; 287(1): C218 - C234.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Q. Wang, X. Wang, and B. M. Evers
Induction of cIAP-2 in Human Colon Cancer Cells through PKC{delta}/NF-{kappa}B
J. Biol. Chem., December 19, 2003; 278(51): 51091 - 51099.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online