Approaches to the pathogenesis of bronchial asthma

本文观察了哮喘小鼠肺和脾组织中SOCS家族基因的表达。肺组织中SOCS-1表达增强，而SOCS-3和SOCS-5表达增强。SOCS-1的表达在第一次攻击时达到高峰，此时IL-4和干扰素-g的mRNA表达达到最高。小鼠脾组织中SOCS基因表达无明显变化。为了探讨SOCS-1的作用，我们检测了外源性SOCS-1/脂质体给药对哮喘模型的影响。与空载体/脂质体注射相比，SOCS-1/脂质体组的嗜酸性炎症明显减轻。此外，在SOCS-1^&lt；+/-&gt；小鼠的哮喘模型中观察到了长期的嗜酸性炎症。这些结果表明SOCS-1参与了嗜酸性气道炎症，并能促进炎症的消退。我们最初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。经高效液相色谱法测定，抑制因子的相对分子质量与未纯化的小鼠IL-10几乎相同。由于加入抗IL-10抗体可中和其抑制活性，因此我们推断该因子为IL-10。这意味着IL-10。是降低哮喘小鼠模型IL-12的最重要的药物。

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.