Cyclic adenosine monophosphate induces plasminogen activator inhibitor-1 expression in human mast cells

Plaminogen activator inhibitor-1 (PAI-1), the key physiological inhibitor of the plasmin fibrinolytic system, plays important roles in the pathogenesis of asthma. Mast cells (MCs) are crucial effector cells and a major source of PAI-1 for asthma. Cyclic adenosine monophosphate (cAMP) is the important regulator of MCs; however, its effects on PAI-1 expression in MCs remain unknown. We reported cAMP/protein kinase A pathway positively regulates PAI-1 expression through cAMP-response element binding protein binding to hypoxia response element-1 at −158 to −153 bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated stimulation.

Research highlights► Cyclic AMP induces plasminogen activator inhibitor-1 (PAI-1) expression in mast cells (MCs). ► The cAMP-response element-binding protein is the key transcription factor. ► The hypoxia response element-1 at −158/−153 bp is the pivotal cis-acting element. ► Cyclic AMP synergistically augments PAI-1 expression in ionomycin- or IgE-stimulated MCs.