Roflumilast N-Oxide in Combination with Formoterol Enhances the Antiinflammatory Effect of Dexamethasone in Airway Smooth Muscle Cells.

摘要: Roflumilast is an orally active phosphodiesterase 4 inhibitor approved for use in chronic obstructive pulmonary disease. N-oxide (RNO) the metabolite of roflumilast and has a demonstrated antiinflammatory impact vivo vitro. To date, effect RNO on synthetic function airway smooth muscle (ASM) cells unknown. We address this herein investigate β2-adrenoceptor-mediated, cAMP-dependent responses ASM vitro, whether enhances steroid-induced repression inflammation. (0.001–1,000 nM) alone had no AMP production from cells, significant potentiation long-acting β2-agonist formoterol-induced cAMP could only be achieved at highest concentration tested (1,000 nM). At concentration, exerted small, but not significantly different, expression mitogen-activated protein kinase phosphatase 1. Consequently, tumor necrosis fact...