| Downregulation of basophil-derived IL-4 and in vivo T(H)2 IgE responses by serotonin and other organic cation transporter 3 ligands. | |
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MedLine Citation:
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PMID: 21636115 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Murine basophils can contribute to the T(H)2 polarization of the immune response by providing rapidly large amounts of IL-4, which suggests that pharmacologic downregulation of this cytokine might provide a strategy to attenuate pathologies associated with excessive production. OBJECTIVE: We examined a number of physiological and pharmacologic ligands of the organic cation transporter 3 (OCT3), a membrane carrier of biogenic amines, for their inhibitory effect on IL-4 production by basophils, selecting the most efficient compounds for in vivo evaluation in basophil-dependent experimental models. METHODS: IL-4 production by basophils isolated ex vivo or from bone marrow cultures was assessed in response to various stimuli with or without biogenic monoamines or pharmacologic analogs. Selected compounds were administered in vivo to examine their effect on levels of circulating IgE generated during a basophil-dependent T(H)2 response and on basophil activation in mice receiving IL-33. RESULTS: We found a drastic decrease in IL-4 production by stimulated basophils on exposure to serotonin (5-hydroxytryptamine [5-HT]) that is taken up by basophils through the specific high-affinity transporters serotonin transporter and the polyspecific, high-capacity organic cation transporter 3 (OCT3; or Slc22a3) but inhibits their function exclusively through the latter. This downregulation is likewise observed in vivo in response to 5-HT and other OCT3 ligands, as well as in human basophils sorted from PMBCs of nonatopic donors. CONCLUSIONS: We provide evidence for a new means of downregulating IL-4 production by basophils, both in vitro and in vivo, through OCT3 targeted by 5-HT and pharmacologic ligands. |
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Authors:
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Elke Schneider; François Machavoine; Rachel Bricard-Rignault; Mélanie Levasseur; Anne France Petit-Bertron; Sophie Gautron; Jean-Antoine Ribeil; Jean-Marie Launay; Salah Mecheri; Francine Côté; Michel Dy |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-31 |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: - ISSN: 1097-6825 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-6-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Université Paris Descartes, Faculté de Médecine, CNRS UMR 8147 "Cytokines, Hematopoiesis and Immune Response," Hôpital Necker, Paris, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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