Increased Th2 Cytokine Secretion, Eosinophilic Airway Inflammation, and Airway Hyperresponsiveness in Neurturin-Deficient Mice
Autor: | Olivia Domingues, François Hentges, Jacques Zimmer, Wim Ammerlaan, Aurélie Poli, Maud Theresine, Nicolaas H. C. Brons, Tatiana Michel |
---|---|
Rok vydání: | 2011 |
Předmět: |
Glial Cell Line-Derived Neurotrophic Factor Receptors
Ovalbumin Neurturin medicine.medical_treatment Immunology Antibodies Allergic inflammation Proinflammatory cytokine Mice Th2 Cells Immune system Neurotrophic factors Animals Immunology and Allergy Medicine Lung Mice Knockout Reverse Transcriptase Polymerase Chain Reaction business.industry respiratory system Eosinophil Flow Cytometry Asthma respiratory tract diseases Eosinophils Mice Inbred C57BL medicine.anatomical_structure Nerve growth factor Cytokine Cytokines Lymph Nodes Bronchial Hyperreactivity business Bronchoalveolar Lavage Fluid |
Zdroj: | The Journal of Immunology. 186:6497-6504 |
ISSN: | 1550-6606 0022-1767 |
Popis: | Neurotrophins such as nerve growth factor and brain-derived neurotrophic factor have been described to be involved in the pathogenesis of asthma. Neurturin (NTN), another neurotrophin from the glial cell line-derived neurotrophic factor family, was shown to be produced by human immune cells: monocytes, B cells, and T cells. Furthermore, it was previously described that the secretion of inflammatory cytokines was dramatically stimulated in NTN knockout (NTN−/−) mice. NTN is structurally similar to TGF-β, a protective cytokine in airway inflammation. This study investigates the implication of NTN in a model of allergic airway inflammation using NTN−/− mice. The bronchial inflammatory response of OVA-sensitized NTN−/− mice was compared with wild-type mice. Airway inflammation, Th2 cytokines, and airway hyperresponsiveness (AHR) were examined. NTN−/− mice showed an increase of OVA-specific serum IgE and a pronounced worsening of inflammatory features. Eosinophil number and IL-4 and IL-5 concentration in the bronchoalveolar lavage fluid and lung tissue were increased. In parallel, Th2 cytokine secretion of lung draining lymph node cells was also augmented when stimulated by OVA in vitro. Furthermore, AHR was markedly enhanced in NTN−/− mice after sensitization and challenge when compared with wild-type mice. Administration of NTN before challenge with OVA partially rescues the phenotype of NTN−/− mice. These findings provide evidence for a dampening role of NTN on allergic inflammation and AHR in a murine model of asthma. |
Databáze: | OpenAIRE |
Externí odkaz: |