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 -153bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated stimulation.
Ma
Zhongcai
Z
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Torrance, CA 90502, USA. zcma@labiomed.org
Kwong
Kenny Y C
KY
Tovar
Jason P
JP
Paek
David
D
D001249:Asthma / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017455:Receptors, IgE / Q000378:metabolism; D020218:Response Elements
D017362:Cyclic AMP Response Element-Binding Protein; D017395:Plasminogen Activator Inhibitor 1; D017455:Receptors, IgE; C051321:SERPINE1 protein, human; D000242:Cyclic AMP; D002118:Calcium