Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation
| Autor: | Bruno Gomes, Catherine Leclerc, Pierre Paulet, Bernard Mariamé, Marilena Djata Cabral, Jean-Charles Guéry, Alexandra Gallard, Marc Moreau, Philippe Druet, Magali Savignac, Lucette Pelletier |
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| Přispěvatelé: | 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) |
| Rok vydání: | 2007 |
| Předmět: |
MESH: Inflammation
CD4-Positive T-Lymphocytes Intracellular Fluid MESH: Asthma medicine.medical_treatment MESH: Calcium Channel Blockers Critical Care and Intensive Care Medicine Lymphocyte Activation Severity of Illness Index Mice 0302 clinical medicine MESH: Animals MESH: Administration Intranasal Lung 0303 health sciences Mice Inbred BALB C biology MESH: Dendritic Cells MESH: Intracellular Fluid MESH: Enzyme-Linked Immunosorbent Assay MESH: CD4-Positive T-Lymphocytes respiratory system Calcium Channel Blockers 3. Good health medicine.anatomical_structure Cytokine MESH: Calcium Female medicine.symptom Bronchoalveolar Lavage Fluid MESH: Injections Intraperitoneal Injections Intraperitoneal medicine.drug Pulmonary and Respiratory Medicine MESH: Mice Transgenic Ovalbumin Nicardipine MESH: Mice Inbred BALB C Inflammation Enzyme-Linked Immunosorbent Assay Mice Transgenic MESH: Nicardipine 03 medical and health sciences Th2 Cells MESH: Th2 Cells Intensive care MESH: Severity of Illness Index MESH: Cell Proliferation medicine Animals MESH: Lung [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Lymphocyte Activation MESH: Mice B cell Interleukin 4 Administration Intranasal 030304 developmental biology Cell Proliferation MESH: Ovalbumin business.industry MESH: Bronchoalveolar Lavage Fluid T lymphocyte Dendritic Cells Asthma respiratory tract diseases Disease Models Animal Immunology biology.protein Calcium MESH: Disease Models Animal business MESH: Female 030215 immunology |
| Zdroj: | 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⟩ |
| ISSN: | 1073-449X 1535-4970 |
| DOI: | 10.1164/rccm.200607-1026OC⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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