To investigate the role of interleukin-31 in ovalbumin-induced airway hyper-responsive mice
| Autor: | Cheng-Chi Chan, 詹政己 |
|---|---|
| Rok vydání: | 2006 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 94 Asthma is a complex pulmonary inflammatory disease. Generally, it is believed that the susceptible individuals have an abnormal immune response to inhaled allergens. According to the previous studies, Th2 cells and their cytokines, IL-4, IL-5, and IL-13 play a pivotal role in the pathogenesis of asthma. These Th2 cytokines cause the differentiation, recruitment, and activation of the mast cells and eosinophils in the airway mucosa. Activation of these cells releases a large number of proinflammatory mediators which induce bronchial obstruction, airway hyper-responsiveness, and airway inflammation. Recently, a novel four-helix bundle cytokine, IL-31, has been identified. IL-31 is expressed mainly by activated T cells, produced particularly in larger amount in Th2 than Th1 cells. IL-31 induces similar symptoms of dermatitis in mice. Clinically, nearly 80% children with atopic dermatitis develop allergic rhinitis or asthma. IL-31 signals via the heterodimeric receptor complex composed of IL-31 RA and OSMR. However, the exact biological functions of IL-31 aren’t fully understood. Besides in epithelial cells and keratinocytes, IL-31 receptors are up-regulated in lung epithelium and bronchoalveolar lavage cells from an animal model of OVA-challenged airway hyper-responsiveness. Thus, we would like to evaluate whether IL-31 plays a role in the pathogenesis of asthma. We first cloned IL-31 cDNA from activated splenocytes and constructed into the eukaryotic pcDNA3.1/mIL-31 expression vector. Normal mice were injected intramuscularly by pcDNA3.1/mIL-31 at days 0 and 7. Increased numbers of lymphocytes in BALF were significantly detected from IL-31 administrated mice. We further used OVA as an allergen to induce an asthmatic animal model; the sensitized mice were injected intramuscularly by pcDNA3.1/mIL-31 at days 13 and 20. The expression of IL-31 and receptor genes in BALF cells and lung tissues of OVA-sensitized mice was analyzed by RT-PCR. The OVA-specific antibody from serum and Th2 cytokines from OVA-treated splenocytes were quantified by ELISA. Nevertheless, the levels of IL-31 and OSMR in lung tissues between normal mice and OVA-sensitized mice were not different. IL-31 RA in the lung tissues and BALF cells of OVA-sensitized mice expressed significantly higher levels than normal mice. The titers of OVA-specific antibody between normal and OVA-sensitized mice were not different. Elevated Th2 cytokines were expressed in splenocytes of pcDNA3.1/mIL-31 injected OVA-sensitized mice. Our data suggest that IL-31 may enhance the pathogenesis of asthma through higher expression of IL-31 RA in OVA-sensitized mice |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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