Abstract
The epithelial barrier is a protective layer against unwanted particles, present in cigarette smoke (CS), a risk factor for developing chronic obstructive pulmonary disease. cAMP, a second messenger, increases barrier properties in endothelial cells, but the role of cAMP in the epithelial barrier is not known. The cAMP effectors, PKA and Epac, may be involved, next to compartmentalization of cAMP signalling by A‐kinase anchoring proteins (AKAPs). Our hypothesis is that AKAPs are involved in CS‐induced effects on the maintenance of the barrier dysfunction. We studied the effect of cigarette smoke extract (CSE) on the barrier function by electrical cell‐substrate impedance sensing (ECIS) and by analyzing the main cell‐cell contact molecule E‐cadherin. CSE‐induced reduction of the functional epithelial barrier is independently of both PKA and Epac. Addition of Ht31 (AKAP‐inhibitor) prevented the effects of CSE on the barrier, strongly suggesting that compartmentalization of cAMP by AKAPs maintains the barrier properties. In addition CSE delocalizes E‐cadherin and AKAP9 from the membrane and reduces the expression of these proteins. Ht31 relocalizes and restores E‐cadherin and AKAP9 levels. Similar results on AKAP9 were obtained in primary epithelial cells from current smokers. In conclusion, AKAPs contribute to CSE‐induced disturbance of the epithelial barrier by translocation of E‐cadherin from the cell membrane. (NAF grant 3.2.09.034)
Published Version
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