AJP - GI Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Am J Physiol Gastrointest Liver Physiol (December 27, 2002). doi:10.1152/ajpgi.00214.2002
This Article
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
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
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 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.
Submitted on June 6, 2002
Accepted on December 16, 2002

Bryostatin-1 Attenuates TNF-Induced Epithelial Barrier Dysfunction: Role of novel PKC isozymes

James Yoo1, Anthony Nichols2, Jaekyung C. Song3, Joshua Mammen2, Isabel Calvo3, Roger Worrell2, John Cuppoletti2, Karl Matlin3, and Jeffrey B. Matthews3*

1 Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
2 Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio, USA
3 Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio, USA; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: jeffrey.matthews{at}uc.edu.

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 pre-treatment with bryostatin-1, a PKC agonist. Based on a pattern of sensitivity to pharmacologic inhibitors of PKC, this epithelial barrier preservation was mediated by novel PKC isozymes. Bryostatin-1 reduced TNF receptor (TNF-R1) surface availability, based on radio-labeled 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 based on mutual co-immunoprecipitation 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.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1979 by the American Physiological Society.