Approaches to the pathogenesis of bronchial asthma

支气管哮喘发病机制的探讨

• 批准号: 13670603
• 负责人: YOKOYAMA Akihito
• 金额: $ 2.37万
• 依托单位: HIROSHIMA UNIVERSIlY (2003)Ehime University (2001-2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670603/
• 关键词: cytokine; bronchial asthma; eosinophil; interleukin; SOCS; IL-12; IL-10; 転写因子; 悪性中皮腫

Expression of SOCS family mRNA was examined in lung and spleen in a mouse model of asthma. Augmented expression of SOCS-1 but not SOCS-3 and SOCS-5 was observed in the lung. The expression of SOCS-1 was peaked in the first challenge, when maximum expressions of IL-4 and IFN-g mRNA were observed. The SOCS mRNA expressions were not changed in the spleen. To explore the role of SOCS-1, we examined the effects of exogenous administration of SOCS-1/liposome to the asthma model. The eosinophilic inflammation was significantly diminished following SOCS-1/liposome in comparison with null/liposome administration. Furthermore, prolonged eosinophilic inflammation was observed in an asthma model in SOCS-1^<+/-> mice. These results indicated that SOCS-1 is involved in eosinophilic airway inflammation, and it could promote resolution. of the inflammation.We originally observed IL-12 inhibitory factor in the supernatants from antigen-stimulated splenic T cells obtained from asthma model mice. The estimated molecular weight of inhibitory factor was almost equal to naive mouse IL-10 by HPLC. Since the inhibitory activity was neutralized by addition of anti-IL-10 antibody, we concluded that the factor is IL-10. This means IL-10. is the most important for diminishing IL-12 in mouse model of asthma.

在哮喘小鼠模型中检测SOCS家族mRNA在肺和脾中的表达。在肺中观察到SOCS-1而非SOCS-3和SOCS-5的表达增强。SOCS-1的表达在第一次攻击时达到高峰，此时观察到IL-4和IFN-gmRNA的最大表达。SOCS mRNA在脾脏中的表达无明显变化。为了探讨SOCS-1的作用，我们检测了外源性施用SOCS-1/脂质体对哮喘模型的影响。与空白/脂质体施用相比，在SOCS-1/脂质体施用后嗜酸性粒细胞炎症显著减少。此外，在SOCS-1^<+/->小鼠的哮喘模型中观察到延长的嗜酸性粒细胞炎症。这些结果表明，SOCS-1参与嗜酸性粒细胞性气道炎症，并且它可以促进消退。我们最初在从哮喘模型小鼠获得的抗原刺激的脾T细胞的上清液中观察到IL-12抑制因子。HPLC法测得抑制因子的分子量与未处理小鼠IL-10的分子量相当。由于通过加入抗IL-10抗体中和了抑制活性，我们得出结论，该因子是IL-10。这意味着IL-10。对哮喘小鼠模型IL-12的降低作用最为重要。

项目成果

Irifune K et al.: "Type 1 helper T cells induce alveolitis but do not lead to pulmonary fibrosis in mice"Eur Respir J. 21. 11-18 (2003)

Irifune K 等人：“1 型辅助 T 细胞在小鼠中诱导肺泡炎，但不会导致肺纤维化”Eur Respir J. 21. 11-18 (2003)

Sakai K, Yokoyama A, Kohno N, Hamada H, Hiwada K: "Prolonged antigen exposure ameliorates airway inflammation but not remodeling in a mouse model of bronchial asthma"Int Arch Allergy Immunol. 126. 126-134 (2001)

Sakai K、Yokoyama A、Kohno N、Hamada H、Hiwada K：“延长抗原暴露可改善支气管哮喘小鼠模型中的气道炎症，但不会重塑”Int Arch Allergy Immunol。

Sakai K et al.: "Prolonged antigen exposure ameliorates airway inflammation but not remodeling in a mouse model of bronchial asthma"Int Arch Allergy Immunol. 126. 126-134 (2001)

Sakai K 等人：“延长抗原暴露可改善支气管哮喘小鼠模型中的气道炎症，但不会重塑”Int Arch AllergyImmunol。

Ohnishi H, Yokoyama A, Yasuhara Y, et al.: "Circulating KL-6 levels in patients with drug induced pneumonitis"Thorax. 58. 872-875 (2003)

Ohnishi H、Yokoyama A、Yasuhara Y 等人：“药物性肺炎患者的循环 KL-6 水平”胸部。

Irifune, K., Yokoyama, A., Kohno, N., Sakai, K., Hiwada, K: "Type 1 helper T cells induce alveolitis but do not lead to pulmonary fibrosis in mice."European Respiratory Jounal. 21・1. 11-18 (2003)

Irifune, K.、Yokoyama, A.、Kohno, N.、Sakai, K.、Hiwada, K：“1 型辅助 T 细胞会诱发小鼠肺泡炎，但不会导致肺纤维化。”欧洲呼吸杂志 21・1。 .11-18 (2003)