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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...

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Autores principales: Eskandari, Nahid, Bastan, Reza, Esfahani, Seyyed Hamid Zarkesh, Peachell, Peter T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513324/
https://www.ncbi.nlm.nih.gov/pubmed/26261827
http://dx.doi.org/10.4103/2277-9175.158040
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author Eskandari, Nahid
Bastan, Reza
Esfahani, Seyyed Hamid Zarkesh
Peachell, Peter T
author_facet Eskandari, Nahid
Bastan, Reza
Esfahani, Seyyed Hamid Zarkesh
Peachell, Peter T
author_sort Eskandari, Nahid
collection PubMed
description 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. MATERIALS AND 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. CONCLUSION: 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.
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spelling pubmed-45133242015-08-10 The effect of cyclic nucleotide analog drugs on the mediators release from basophils Eskandari, Nahid Bastan, Reza Esfahani, Seyyed Hamid Zarkesh Peachell, Peter T Adv Biomed Res Original Article 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. MATERIALS AND 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. CONCLUSION: 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. Medknow Publications & Media Pvt Ltd 2015-06-04 /pmc/articles/PMC4513324/ /pubmed/26261827 http://dx.doi.org/10.4103/2277-9175.158040 Text en Copyright: © 2015 Eskandari. http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Original Article
Eskandari, Nahid
Bastan, Reza
Esfahani, Seyyed Hamid Zarkesh
Peachell, Peter T
The effect of cyclic nucleotide analog drugs on the mediators release from basophils
title The effect of cyclic nucleotide analog drugs on the mediators release from basophils
title_full The effect of cyclic nucleotide analog drugs on the mediators release from basophils
title_fullStr The effect of cyclic nucleotide analog drugs on the mediators release from basophils
title_full_unstemmed The effect of cyclic nucleotide analog drugs on the mediators release from basophils
title_short The effect of cyclic nucleotide analog drugs on the mediators release from basophils
title_sort effect of cyclic nucleotide analog drugs on the mediators release from basophils
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513324/
https://www.ncbi.nlm.nih.gov/pubmed/26261827
http://dx.doi.org/10.4103/2277-9175.158040
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