Cyclic adenosine monophosphate induces plasminogen activator inhibitor-1 expression in human mast cells |
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| Authors: | Zhongcai Ma Kenny Y.C. Kwong David Paek |
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| Affiliation: | a 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
b Department of Pathology, 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 |
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| Abstract: | 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. |
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| Keywords: | AC, adenylate cyclase AHR, airway hyperresponsiveness cAMP, cyclic adenosine monophosphate CRE, cAMP-response element CREB, CRE-binding protein, db-cAMP, dibutyryl cAMP db-cAMP, dibutyryl cAMP DDA, 2&prime ,5&prime -dideoxyadenosine DN, dominant negative EMSA, electrophoretic mobility shift assay HIF, hypoxia-inducible factor HRE-1, hypoxia response element-1 MC, mast cell PAI-1, plasminogen activator inhibitor-1 PKA, protein kinase A tPA, tissue-type plasminogen activator uPA, urokinase-type plasminogen activator USF, upstream stimulatory factor WT, wild-type |
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