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Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation

Authors :
Bruno Gomes
Catherine Leclerc
Pierre Paulet
Bernard Mariamé
Marilena Djata Cabral
Jean-Charles Guéry
Alexandra Gallard
Marc Moreau
Philippe Druet
Magali Savignac
Lucette Pelletier
Centre de Physiopathologie Toulouse Purpan (CPTP)
Université Toulouse III - Paul Sabatier (UT3)
Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Centre de biologie du développement (CBD)
Centre de Biologie Intégrative (CBI)
Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3)
Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3)
Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI)
Source :
American Journal of Respiratory and Critical Care Medicine, American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 2007, 175 (11), pp.1117-24. ⟨10.1164/rccm.200607-1026OC⟩
Publication Year :
2007

Abstract

RATIONALE: Ca(2+) signaling controls the production of T helper (Th) type 2 cytokines known to be deleterious in asthma. Recently, we showed that Ca(2+) signaling was dihydropyridine (DHP)-sensitive in Th2 lymphocytes and that the DHP derivate, nicardipine, used in the treatment of cardiovascular pathologies, prevents Th2-dependent B cell polyclonal activation. OBJECTIVES: We tested the effect of nicardipine in experimental allergic asthma. METHODS: BALB/c mice immunized with ovalbumin (OVA) in alum and challenged with intranasal OVA were treated with nicardipine once the Th2 response, or even airway inflammation, was induced. We also tested the effect of nicardipine in asthma induced by transferring OVA-specific Th2 cells in BALB/c mice exposed to intranasal OVA. We checked the impact of nicardipine on T-cell responses and airway inflammation. MEASUREMENTS AND MAIN RESULTS: Nicardipine inhibited in vitro Ca(2+) response in Th2 cells. In vivo, it impeded the development of Th2-mediated airway inflammation and reduced the capacity of lymphocytes from lung-draining lymph nodes to secrete Th2, but not Th1, cytokines. Nicardipine did not affect antigen presentation to CD4(+) T lymphocytes, nor the initial localization of Th2 cells into the lungs of mice exposed to intranasal OVA; however, it reduced the production of type 2 cytokines and the amplification of the Th2 response in mice with asthma. Conversely, nicardipine had no effect on Th1-mediated airway inflammation. CONCLUSIONS: Nicardipine improves experimental asthma by impairing Th2-dependent inflammation. This study could provide a rationale for developing drugs selectively targeting DHP receptors of Th2 lymphocytes, potentially beneficial in the treatment of asthma.

Details

ISSN :
1073449X and 15354970
Volume :
175
Issue :
11
Database :
OpenAIRE
Journal :
American journal of respiratory and critical care medicine
Accession number :
edsair.doi.dedup.....c53ad3e4682b548428d117f26b46093e
Full Text :
https://doi.org/10.1164/rccm.200607-1026OC⟩