help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 18, 2010, doi:10.1164/rccm.200907-1166OC

Am. J. Respir. Crit. Care Med., Volume 181, Number 12, June 2010, 1310-1317

A more recent version of this article appeared on June 15, 2010
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200907-1166OCv1
181/12/1310    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Djata Cabral, M.
Right arrow Articles by Pelletier, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Djata Cabral, M.
Right arrow Articles by Pelletier, L.

Submitted on July 30, 2009
Accepted on February 17, 2010

Knocking-down Cav1 Calcium Channels Implicated in Th2-cell Activation Prevents Experimental Asthma

Marilena Djata Cabral1, Pierre-Emmanuel Paulet1, Virginie Robert1, Bruno Gomes2, Marie-Laure Renoud2, Magali Savignac3, Catherine Leclerc4, Marc Moreau4, David Lair5, Marie Langelot5, Antoine Magnan5, Hans Yssel6, Bernard Mariame2, Jean-Charles Guery7, and Lucette Pelletier8*

1 Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM), U563, Toulouse, France; Université Paul Sabatier, Toulouse, France; Institut Fédératif de la Recherche Bio-Médicale de Toulouse (I.F.R.-B.M.T.), Tolouse, France; L’institut du thorax, Equipe AVENIR, INSERM U915, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France; L’institut du thorax, Service de Pneumologie, Plate-Forme Transversale d’Allergologie, CHU Nantes, Nantes, France, 2 Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM), U563, Toulouse, France; Université Paul Sabatier, Toulouse, France; Institut Fédératif de la Recherche Bio-Médicale de Toulouse (I.F.R.-B.M.T.), Tolouse, France, 3 Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM), U563, Toulouse, France; Université Paul Sabatier, Toulouse, France; Institut Fédératif de la Recherche Bio-Médicale de Toulouse (I.F.R.-B.M.T.), Tolouse, France; CNRS Groupement de recherche GDR 2688, Toulouse, France, 4 Université Paul Sabatier, Toulouse, France; Centre de Biologie du Développement, Centre National de la Recherche Scientifique CNRS UMR 5547, Toulouse, France; CNRS Groupement de recherche GDR 2688, Toulouse, France, 5 L’institut du thorax, Equipe AVENIR, INSERM U915, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France; L’institut du thorax, Service de Pneumologie, Plate-Forme Transversale d’Allergologie, CHU Nantes, Nantes, France, 6 INSERM, U844, Montpellier, France, 7 Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM), U563, Toulouse, France; Université Paul Sabatier, Toulouse, France; Institut Fédératif de la Recherche Bio-Médicale de Toulouse (I.F.R.-B.M.T.), Tolouse, France; Centre Hospitalier Universitaire, Toulouse, France, 8 Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM), U563, Toulouse, France; Université Paul Sabatier, Toulouse, France; Institut Fédératif de la Recherche Bio-Médicale de Toulouse (I.F.R.-B.M.T.), Tolouse, France; CNRS Groupement de recherche GDR 2688, Toulouse, France; Centre Hospitalier Universitaire, Toulouse, France

* To whom correspondence should be addressed. E-mail: Lucette.Pelletier{at}inserm.fr.

Rationale: T helper 2 (Th2)-cells orchestrate allergic asthma and the cytokines they produce, interleukin (IL)-4, IL-5 and IL-13 are deleterious in allergy. Therefore, it is important to identify key signaling-molecules expressed by Th2-cells that are essential for their function. We have previously shown that dihydropyridines selectively modulate Th2-cell functions. Objectives: Since dihydropyridines bind to and modulate voltage-dependent calcium (Cav1) channel in excitable cells, we aimed at showing that Th2-cells selectively express functional Cav1-related channels, the inhibition of which may prevent asthma. Methods: We looked for Cav1 channel expression in Th2 and Th1-cells by real-time PCR and Western blotting. We sequenced the isoforms expressed by Th2-cells and tested whether Cav1 antisense oligodeoxynucleotides (Cav1AS) affected Ca2+ signaling and cytokine production. Finally, we tested the effect of Cav1AS in the passive asthma model by injection of ovalbumin (OVA)-specific Th2-cells transfected with Cav1AS into BALB/c mice challenged with intranasal OVA and in the active model of asthma by intranasal delivery of Cav1AS together with soluble asthma in BALB/c mice previously immunized with OVA in alum. Measurement and main results: We show that mouse Th2 but not Th1-cells expressed Cav1.2 and Cav1.3 channels. Th2-cells transfected with Cav1AS had impaired Ca2+ signaling and cytokine production, and lost their ability to induce airway inflammation upon adoptive transfer. Furthermore, intranasal administration of Cav1AS suppressed airway inflammation and hyper-reactivity in an active model of asthma. Conclusions: These results indicate that Th2-cells selectively express Cav1 channels that may be efficiently targeted in T-lymphocytes to prevent experimental asthma.
Key words: Th2-cells • voltage-dependent calcium channels • allergic asthma • antisense oligonucleotides






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2010 American Thoracic Society