QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.017251v1 69/2/492    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Everett, R. S. Articles by Johnson, L. G. Search for Related Content PubMed PubMed Citation Articles by Everett, R. S. Articles by Johnson, L. G.

Specific Modulation of Airway Epithelial Tight Junctions by Apical Application of an Occludin Peptide

Cystic Fibrosis/Pulmonary Research and Treatment Center (R.S.E., M.K.V., L.G.J.), and the Departments of Medicine and Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (L.G.J.); and University of Queensland, Brisbane, Australia (N.B., I.T.)

Tight junctions are directly involved in regulating the passage of ions and macromolecules (gate functions) in epithelial and endothelial cells. The modulation of these gate functions to transiently regulate the paracellular permeability of large solutes and ions could increase the delivery of pharmacological agents or gene transfer vectors. To reduce the inflammatory responses caused by tight junction-regulating agents, alternative strategies directly targeting specific tight junction proteins could prove to be less toxic to airway epithelia. The apical delivery of peptides corresponding to the first extracellular loop of occludin to transiently modulate apical paracellular flux has been demonstrated in intestinal epithelia. We hypothesized that apical application of these occludin peptides could similarly modulate tight junction permeability in airway epithelia. Thus, we investigated the effects of apically applied occludin peptide on the paracellular permeability of molecular tracers and viral vectors in well differentiated human airway epithelial cells. The effects of occludin peptide on cellular toxicity, tight junction protein expression and localization, and membrane integrity were also assessed. Our data showed that apically applied occludin peptide significantly reduced transepithelial resistance in airway epithelia and altered tight junction permeability in a concentration-dependent manner. These alterations enhanced the paracellular flux of dextrans as well as gene transfer vectors. The occludin peptide redistributed occludin but did not alter the expression or distribution of ZO-1, claudin-1, or claudin-4. These data suggest that specific targeting of occludin could be a better-suited alternative strategy for tight junction modulation in airway epithelial cells compared with current agents that modulate tight junctions.

Address correspondence to: Dr. Larry G. Johnson, Professor of Medicine and Director, Pulmonary and Critical Care Medicine, The University of Arkansas for Medical Sciences, 4301 W. Markham St., Mail Slot 555, Little Rock, AR 72205. E-mail lgjohnson{at}uams.edu

This article has been cited by other articles:

				R. J. Mrsny, G. T. Brown, K. Gerner-Smidt, A. G. Buret, J. B. Meddings, C. Quan, M. Koval, and A. Nusrat A Key Claudin Extracellular Loop Domain is Critical for Epithelial Barrier Integrity Am. J. Pathol., April 1, 2008; 172(4): 905 - 915. [Abstract] [Full Text] [PDF]

				B. L. Daugherty, C. Ward, T. Smith, J. D. Ritzenthaler, and M. Koval Regulation of Heterotypic Claudin Compatibility J. Biol. Chem., October 12, 2007; 282(41): 30005 - 30013. [Abstract] [Full Text] [PDF]