Modulation of cellular transport characteristics of the human lung alveolar epithelia

Among the drug delivery and targeting (ddt) routes, lung alveolar epithelium has beengiven enormous attentions in terms of the delivery of a wide range of macromolecules suchas gene- or protein-based nanopharmaceuticals. however, little is known about cellularmodulation of lung transport characteristics by endogenous and/or exogenous agents. thus, inthe current study, impact ofdexamethasone (dex), which is a customary additive to the culturemedia ofalveolar epithelial cells, was assessed with respect to some transport properties of thehuman adenocarcinoma a549 cells, which is a well-known cell-based in vitro model for lungepithelia. to achieve such goal, we studied the trans epithelial electrical resistance (teer)and barrier restrictiveness using the paracellular marker, mannitol. further more, the effect ofdex on the expression of clathrin, the main integral protein of clathrin coated pits, as well asdynamin (gtp binding protein essential for the vesicle budding off process) were assessed.a549 cells treated with dex displayed distinct phenotypic and growth changes, also resulingin higher teer values (~ 100 n.cm2) compared to the untreated cells (~ 45 n.cm2) . suchparacellular tightness properties were also confirmed by mannitol permeability assay, showinga marked difference in the permeability coefficient between untreated and dex-treated a549cells, i.e., 7.83(plus-minus) 0.3.7 (x 10-6 crn.s') and 3.46 (plus-minus) 0.22 (x 10-6 cm.sl), respectively. althoughdex exerted little impact on expression of the clathrin mrna, it elicited a significantincrease in dynamin protein expression. therefore, it is proposed that dex supplementationof alveolar epithelial a549 cells culture media may confer a better model for pulmonaryddt investigations. however, more extensive work is needed to be carried out in order toclarify the precise role of dex in cellular transport of macromolecules via receptor-mediatedendocytosis/transcytosis.