Agonist binding to b-adrenergic receptors on XXXX airway epithelial cells inhibits migration and wound repair.

@entity1 @entity268 @entity2162 @entity5174 @entity1425 @entity3045 @entity1405 @entity35341 @entity3044
UNASSIGNED: @entity1 airway epithelial cells express b-adrenergic receptors (b-ARs), which regulate mucociliary clearance by stimulating transepithelial anion transport and ciliary beat frequency. Previous studies using airway epithelial cells showed that stimulation with @entity3044 increased cell migration and wound repair by a @entity268 -dependent mechanism. In the present study, impedance-sensing arrays were used to measure cell migration and epithelial restitution following wounding of confluent normal @entity1 bronchial epithelial (NHBE) and @entity1 cells by electroporation. Stimulation with @entity1425 or the @entity2162 -selective agonist @entity3045 significantly delayed wound closure and reduced the mean surface area of lamellipodia protruding into the wound. Treatment with the @entity2162 bias agonist @entity1405 or @entity35341 also produced a delay in epithelial restitution similar in magnitude to @entity1425 and @entity3045 . Measurements of extracellular signal-regulated kinase phosphorylation following @entity3045 or @entity1405 stimulation showed no significant change in the level of phosphorylation compared with untreated control cells. However, inhibition of protein phosphatase 2A activity completely blocked the delay in wound closure produced by @entity2162 agonists. In @entity1 cells, where @entity5174 expression was inhibited by RNAi, @entity3045 did not inhibit wound repair, suggesting that @entity2162 agonist stimulation and loss of @entity5174 function share a common pathway leading to inhibition of epithelial repair. Confocal images of the basal membrane of @entity1 cells labeled with anti-b1-integrin (clone HUTS-4) antibody showed that treatment with @entity1425 or @entity1405 reduced the level of activated integrin in the membrane. These findings suggest that treatment with @entity2162 agonists delays airway epithelial repair by a G protein- and @entity268 -independent mechanism involving protein phosphatase 2A and a reduction in b1-integrin activation in the basal membrane.
