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Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation
- 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.
- Subjects :
- 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
Subjects
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⟩