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Acute mechanism of medium chain fatty acid-induced enhancement of airway epithelial permeability.
J Pharmacol Exp Ther. 2003 May; 305(2):440-50.JP

Abstract

The localization of viral receptors to the basolateral surface of airway epithelia is an obstacle to the effectiveness of luminal viral-mediated gene transfer to the lung. The tight junction (TJ) serves as a rate-limiting barrier to the penetration of viral vectors. We have previously identified the sodium salt of the medium chain fatty acid (MCFA) capric acid (C10) as an agent that can enhance the ability of adenoviral vectors to transduce well differentiated (WD) primary human airway epithelial (HAE) cells. Previous studies have suggested that intracellular calcium (Ca(i)2+) levels may play a central role in the long-term C10-mediated increases in junctional permeability. In this study, we investigated the effects of C10 and lauric acid (C12) on Ca(i)2+ in WD primary HAE cells and determined whether these effects were necessary for the acute MCFA-induced reduction in transepithelial resistance (R(T)) and increased permeability. In addition, we characterized the effects of C10 and C12 on components localized to the TJ, including ZO-1, junctional adhesion molecule (JAM), and the claudin family of transmembrane proteins. In addition to rapidly decreasing R(T), C10 and C12 increased cellular and paracellular permeability. C10 induced a rapid, sustained increase in Ca(i)2+. However, buffering Ca(i)2+ did not block the effects of C10 on R(T). Both C10 and C12 caused reorganization of claudins-1, -4, JAM, and beta-catenin, but not ZO-1. These data suggest that C10 and C12 exert their acute effects on airway TJs via a Ca(2+)-independent mechanism of action and may alter junctional permeability via direct effects on the claudin family of TJ proteins.

Authors+Show Affiliations

Cystic Fibrosis/Pulmonary Research and Treatment Center, 7123A Thurston Bowles Bldg., CB no. 7248, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12606647

Citation

Coyne, Carolyn B., et al. "Acute Mechanism of Medium Chain Fatty Acid-induced Enhancement of Airway Epithelial Permeability." The Journal of Pharmacology and Experimental Therapeutics, vol. 305, no. 2, 2003, pp. 440-50.
Coyne CB, Ribeiro CM, Boucher RC, et al. Acute mechanism of medium chain fatty acid-induced enhancement of airway epithelial permeability. J Pharmacol Exp Ther. 2003;305(2):440-50.
Coyne, C. B., Ribeiro, C. M., Boucher, R. C., & Johnson, L. G. (2003). Acute mechanism of medium chain fatty acid-induced enhancement of airway epithelial permeability. The Journal of Pharmacology and Experimental Therapeutics, 305(2), 440-50.
Coyne CB, et al. Acute Mechanism of Medium Chain Fatty Acid-induced Enhancement of Airway Epithelial Permeability. J Pharmacol Exp Ther. 2003;305(2):440-50. PubMed PMID: 12606647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute mechanism of medium chain fatty acid-induced enhancement of airway epithelial permeability. AU - Coyne,Carolyn B, AU - Ribeiro,Carla M P, AU - Boucher,Richard C, AU - Johnson,Larry G, Y1 - 2003/02/11/ PY - 2003/2/28/pubmed PY - 2003/5/31/medline PY - 2003/2/28/entrez SP - 440 EP - 50 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 305 IS - 2 N2 - The localization of viral receptors to the basolateral surface of airway epithelia is an obstacle to the effectiveness of luminal viral-mediated gene transfer to the lung. The tight junction (TJ) serves as a rate-limiting barrier to the penetration of viral vectors. We have previously identified the sodium salt of the medium chain fatty acid (MCFA) capric acid (C10) as an agent that can enhance the ability of adenoviral vectors to transduce well differentiated (WD) primary human airway epithelial (HAE) cells. Previous studies have suggested that intracellular calcium (Ca(i)2+) levels may play a central role in the long-term C10-mediated increases in junctional permeability. In this study, we investigated the effects of C10 and lauric acid (C12) on Ca(i)2+ in WD primary HAE cells and determined whether these effects were necessary for the acute MCFA-induced reduction in transepithelial resistance (R(T)) and increased permeability. In addition, we characterized the effects of C10 and C12 on components localized to the TJ, including ZO-1, junctional adhesion molecule (JAM), and the claudin family of transmembrane proteins. In addition to rapidly decreasing R(T), C10 and C12 increased cellular and paracellular permeability. C10 induced a rapid, sustained increase in Ca(i)2+. However, buffering Ca(i)2+ did not block the effects of C10 on R(T). Both C10 and C12 caused reorganization of claudins-1, -4, JAM, and beta-catenin, but not ZO-1. These data suggest that C10 and C12 exert their acute effects on airway TJs via a Ca(2+)-independent mechanism of action and may alter junctional permeability via direct effects on the claudin family of TJ proteins. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12606647/Acute_mechanism_of_medium_chain_fatty_acid_induced_enhancement_of_airway_epithelial_permeability_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12606647 DB - PRIME DP - Unbound Medicine ER -