A murine IL-4 receptor antagonist that inhibits IL-4- and IL-13-induced responses prevents antigen-induced airway eosinophilia and airway hyperresponsiveness
| Autor: | Erwin W. Gelfand, G Cieslewicz, R. Gundel, M.-C. Shanafelt, J. C. Pratt, Catherine Duez, Anthony Joetham, Adrian Tomkinson |
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| Rok vydání: | 2001 |
| Předmět: |
Immunoglobulin E
Epithelium Leukocyte Count Mice Mutant protein Antibody Specificity T-Lymphocyte Subsets Immunology and Allergy Eosinophilia Phosphorylation Receptor Lung Cells Cultured STAT6 Mice Inbred BALB C Interleukin-13 respiratory system Recombinant Proteins Interleukin 13 Cytokines Female medicine.symptom Bronchial Hyperreactivity Bronchoalveolar Lavage Fluid Immunosuppressive Agents Injections Intraperitoneal Ovalbumin Injections Subcutaneous Immunology B-Lymphocyte Subsets Down-Regulation Biology Immunophenotyping medicine Animals Humans Pulmonary Eosinophilia Interleukin 4 Antagonist respiratory tract diseases Receptors Interleukin-4 Eosinophils Mucus biology.protein Macrophages Peritoneal Trans-Activators Interleukin-4 STAT6 Transcription Factor Spleen |
| Zdroj: | ResearcherID |
| ISSN: | 0022-1767 |
| Popis: | The closely related Th2 cytokines, IL-4 and IL-13, share many biological functions that are considered important in the development of allergic airway inflammation and airway hyperresponsiveness (AHR). The overlap of their functions results from the IL-4R α-chain forming an important functional signaling component of both the IL-4 and IL-13 receptors. Mutations in the C terminus region of the IL-4 protein produce IL-4 mutants that bind to the IL-4R α-chain with high affinity, but do not induce cellular responses. A murine IL-4 mutant (C118 deletion) protein (IL-4R antagonist) inhibited IL-4- and IL-13-induced STAT6 phosphorylation as well as IL-4- and IL-13-induced IgE production in vitro. Administration of murine IL-4R antagonist during allergen (OVA) challenge inhibited the development of allergic airway eosinophilia and AHR in mice previously sensitized with OVA. The inhibitory effect on airway eosinophilia and AHR was associated with reduced levels of IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluid as well as reduced serum levels of OVA-IgE. These observations demonstrate the therapeutic potential of IL-4 mutant protein receptor antagonists that inhibit both IL-4 and IL-13 in the treatment of allergic asthma. |
| Databáze: | OpenAIRE |
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