IntroductionIn asthma, one of die main consequence of the chronical airway inflammation is die epithelial damage and tight junction (TJ) disruption. Airway epithelium is also the prime target for inhaled respiratory drugs including glucocorticoids. Glucocorticoids are anti-inflammatory molecules classically described as acting through a genomic pathway. Similar to many steroid hormones, glucocorticoids also induced rapid non-genomic responses. We recently reported that the synthetic glucocorticoid dexamethasone produced a rapid non-genomic anti-secretory effect on l6HBE14o- monolayers. In the present study, we investigated the potential rapid effect of dexamethasone on TJ formation.MethodsWe used western blotting, immunofluorescence and trans-epithelial resistance (TER) measurement on bronchial airway epithelial cells (16HBEl4o- cell line) in order to investigate the TJ components synthesis (ZO-1 and Claudin-1), expression at the plasma-mebrane and function, respectively. A Peptag assay has been used to tested the effect of dexamethasone on cAMP-dependant protein kinase activity.ResultsThree days exposure to dexamethasone (10^-8M) significantly increased the trans-epithelial resistance of confluent 16HBE14o- cell monolayers through a mechanism involving the classical glucocorticoid receptor. Using western blotting, we have shown that dexamethasone (10^-8M) increased the synthesis of claudin-1 but not ZO-1 However, we reported here that dexamethasone stimulated in less than 10 min ZO-1 expression at the plasma-membrane. The stimulation of ZO-1 expression by dexamethasone was decreased by inhibitors of cAMP-dependant protein kinase activity. In addition, dexamethasone stimulated the cAMP-dependant protein kinase activity.ConclusionThese results provided evidence for a novel rapid non-genomic effects of dexamethasone on TJ formation involving the classical glucocoticoid recepor and a cAMP-dependant protein kinase pathway. Our experiments indicated that the effect of dexamethasone on TJ formation involved the synthesis of claudin-1 but not of ZO-1.