Role of cyclic 3',5'-adenosine monophosphate in the regulation of chemical mediator release and cytokine production from cultured human mast cells
Summary
This summary is machine-generated.Cyclic adenosine monophosphate (cAMP) elevation inhibits human mast cell mediator release and cytokine production. Beta-agonists and some phosphodiesterase inhibitors suppress these responses, with theophylline acting independently.
Area Of Science
- Immunology
- Cell Biology
- Pharmacology
Background
- Cultured human mast cells mimic lung mast cells in protease, histamine release, and drug response.
- Human mast cells play a key role in allergic and inflammatory responses.
Purpose Of The Study
- To determine the role of cyclic 3',5'-adenosine monophosphate (cAMP) in regulating chemical mediator and cytokine release from human mast cells.
- To investigate the effects of cAMP-elevating agents on IgE-mediated responses.
Main Methods
- Cultured human mast cells were treated with cAMP-elevating agents (beta-agonists, phosphodiesterase inhibitors, dibutyryl cAMP).
- IgE-mediated release of histamine, leukotrienes, and PGD2 was measured.
- Production of cytokines (GM-CSF, IL-5, macrophage inflammatory protein-1alpha) was assessed.
- Intracellular cAMP levels were correlated with mediator and cytokine inhibition.
Main Results
- Beta-agonists suppressed IgE-mediated release of histamine, leukotrienes, PGD2, and production of GM-CSF, IL-5, and macrophage inflammatory protein-1alpha.
- Phosphodiesterase inhibitors (theophylline, rolipram, cilostazol) suppressed cytokine production but not chemical mediators.
- Dibutyryl cAMP inhibited both chemical mediator release and cytokine production.
- cAMP elevation correlated with inhibition of histamine and GM-CSF production.
Conclusions
- cAMP elevation is likely responsible for the inhibitory effects of beta-agonists, rolipram, and cilostazol on mast cell mediator and cytokine release.
- Theophylline may inhibit GM-CSF production through a cAMP-independent pathway.
View abstract on PubMed