IL-13-dependent autocrine signaling mediates altered responsiveness of IgE-sensitized airway smooth muscle
| Autor: | Hakon Hakonarson, M. Chen, Michael M. Grunstein, Judith S. Grunstein, Sing Chuang, R. Whelan, J. Leiter |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Pulmonary and Respiratory Medicine
Physiology medicine.medical_treatment Cholinergic Agents In Vitro Techniques Immunoglobulin E Pathogenesis Physiology (medical) medicine Animals Humans Protein Isoforms RNA Messenger Autocrine signalling Receptor Interleukin-13 biology Muscle Smooth Cell Biology respiratory system Acetylcholine Receptors Interleukin-4 respiratory tract diseases Trachea Autocrine Communication medicine.anatomical_structure Cytokine Immunology Interleukin 13 biology.protein Immunization Interleukin-4 Rabbits Interleukin-5 Signal transduction Signal Transduction Respiratory tract |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 282:L520-L528 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00343.2001 |
| Popis: | In testing the hypothesis that interleukin-4 receptor alpha-subunit (IL-4R alpha)-coupled signaling mediates altered airway smooth muscle (ASM) responsiveness in the atopic sensitized state, isolated rabbit tracheal ASM segments were passively sensitized with immunoglobulin E (IgE) immune complexes, both in the absence and presence of an IL-4R alpha blocking antibody (anti-IL-4R alpha Ab). Relative to control ASM, IgE-sensitized tissues exhibited enhanced isometric constrictor responses to administered ACh and attenuated relaxation responses to isoproterenol. These proasthmatic-like effects were prevented in IgE-sensitized ASM that were pretreated with anti-IL-4R alpha Ab. In complementary experiments, IgE-sensitized cultured human ASM cells exhibited upregulated expression of IL-13 mRNA and protein, whereas IL-4 expression was undetected. Moreover, extended studies demonstrated that 1) exogenous IL-13 administration to naïve ASM elicited augmented contractility to ACh and impaired relaxation to isoproterenol, 2) these effects of IL-13 were prevented by pretreating the tissues with an IL-5 receptor blocking antibody, and 3) IL-13 administration induced upregulated mRNA expression and release of IL-5 protein from cultured ASM cells. Collectively, these findings provide new evidence demonstrating that the altered responsiveness of IgE-sensitized ASM is largely attributed to activation of an intrinsic Th2-type autocrine mechanism involving IL-13/IL-4R alpha-coupled release and action of IL-5 in the sensitized ASM itself. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|