Modulation of cellular transport characteristics of the human lung alveolar epithelia

authors:

avatar Jaleh Barar 1 , 2 , * , avatar Ali Maleki 1 , 2 , avatar Yadollah Omidi 1 , 2

Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
Iranian Journal of Pharmaceutical Research: Vol.5, issue 3; 163-171
published online: November 20, 2010
article type: Research Article
received: June 21, 2005
accepted: December 21, 2005
DOI: https://doi.org/10.22037/ijpr.2010.671

how to cite: Barar J, Maleki A, Omidi Y. Modulation of cellular transport characteristics of the human lung alveolar epithelia. Iran J Pharm Res. 2006;5(3):e128281. https://doi.org/10.22037/ijpr.2010.671.

Abstract

Among the drug delivery and targeting (DDT) routes, lung alveolar epithelium has been given enormous attentions in terms of the delivery of a wide range of macromolecules such as gene- or protein-based nanopharmaceuticals. However, little is known about cellular modulation of lung transport characteristics by endogenous and/or exogenous agents. Thus, in the current study, impact of dexamethasone (DEX), which is a customary additive to the culture media of alveolar epithelial cells, was assessed with respect to some transport properties of the human adenocarcinoma A549 cells, which is a well-known cell-based in vitro model for lung epithelia. To achieve such goal, we studied the trans epithelial electrical resistance (TEER) and barrier restrictiveness using the paracellular marker, mannitol. Further more, the effect of DEX on the expression of clathrin, the main integral protein of clathrin coated pits, as well as dynamin (GTP binding protein essential for the vesicle budding off process) were assessed. A549 cells treated with DEX displayed distinct phenotypic and growth changes, also resuling in higher TEER values (~ 100 Ω.cm2) compared to the untreated cells (~ 45 Ω.cm2). Such paracellular tightness properties were also confirmed by mannitol permeability assay, showing a marked difference in the permeability coefficient between untreated and DEX-treated A549 cells, i.e., 7.83± 0.3.7 (× 10-6 cm.s-1) and 3.46 ± 0.22 (× 10-6 cm.s-1), respectively. Although DEX exerted little impact on expression of the clathrin mRNA, it elicited a significant increase in dynamin protein expression. Therefore, it is proposed that DEX supplementation of alveolar epithelial A549 cells culture media may confer a better model for pulmonary DDT investigations. However, more extensive work is needed to be carried out in order to clarify the precise role of DEX in cellular transport of macromolecules via receptor-mediated endocytosis/transcytosis.