The effect of cyclic nucleotide analog drugs on the mediators release from basophils.
BACKGROUND
The cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), are intracellular second messengers that play an important role in modulating inflammatory cells involved in allergic diseases. In general, cAMP suppresses the activity of immune and inflammatory cells. We aim to evaluate the roles of cAMP and cGMP in regulating basophil activity.


METHODS
Basophil-enriched preparations were incubated with analogs and then challenged with anti-IgE or IL-3 (4 or 24 hours). Supernatants were assayed for histamine, IL-4, and IL-13 release. The effects of Sp-8-CPT-cAMPS and Sp-8-CPT-cGMPS on IL-3-dependent mediator release from basophils were determined. The cells were pre-incubated with an analog and then incubated with IL-3 for 24 hours.


RESULTS
Sp-8-CPT-cAMPS was an effective (P < 0.05) inhibitor of IL-4, IL-13, and histamine release from basophils. However, paradoxically, Sp-8-CPT-cGMPS enhanced histamine release and IL-13 generation, but by contrast, had little effect on IL-4 generation. Sp-8-CPT-cGMPS inhibited cytokine generation, but enhanced the release of histamine release to a modest extent.


CONCLUSIONS
This study shows that the cAMP/protein kinase A (PKA) pathway may be inhibitory to the IgE- and non-IgE-dependent release of mediators from basophils.
Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Nahid
N
Eskandari
Razi Karaj Institute, Karaj, Iran.
Reza
R
Bastan
Department of Immunology, Cellular and Molecular Immunology Research Center, Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Seyyed Hamid Zarkesh
SH
Esfahani
Department of Respiratory Medicine, University of Sheffield, United Kingdom.
Peter T
PT
Peachell
Allergy; basophils; cytokine; drug