Dexmedetomidine inhibits apoptosis and expression of COX-2 induced by lipopolysaccharide in primary human alveolar epithelial type 2 cells.

Alveolar epithelial type II cells (ATII cells) are the main target cells being damaged and releasing the inflammatory mediators during acute respiratory distress syndrome (ARDS). Extensive apoptosis of epithelial cells leads to the breakdown of the alveolar-epithelial barrier in ARDS. Cyclooxygenase-2 (COX-2) plays an important role in pulmonary inflammatory response. Dexmedetomidine (DEX), a potent selective α2 adrenergic receptor (α2-AR) agonist, presents sedative, anxiolytic, and analgesic effects for anesthetic procedures. DEX has anti-apoptotic and anti-inflammatory properties. Our study demonstrated that DEX exerted anti-apoptotic effect on primary human epithelial cells with the inhibition of caspase activation, which was partly via the α2AR/PI3K/AKT pathway. Moreover, DEX significantly reduced the expression of COX-2 as well as prostaglandinE2 (PGE2) and tumor necrosis factor-α (TNF-α) production induced by lipopolysaccharide (LPS). Our next step is to determine whether DEX can regulate apoptosis in animal models. These results suggest DEX may be a promising therapy for preventing and treating ARDS as well as chronic diseases by directly targeting epithelial cell actions.