骨髓间充质干细胞通过分泌半乳凝素-1抑制哮喘气道炎症的机制研究

Recent studies have shown that mesenchymal stem cells ( MSCs) ameliorate airway inflammation and airway hyperresponsiveness in asthma. However,beneficial mechanism of MSCs in asthma is unclear.Previous studies indicated that galectin-1 secreted from MSCs had immunosuppressive properties. Moreover, infusion galectin-3 remarkably attenuated the severity of airway inflammation in asthma. Therefore, we hypothesize that protective effect of MSCs in asthma predominantly attribute to gal-1 by suppression dendritic cell function. In this study, MSCs and DC are cocultured in directly and indirectly way and the effect of gal-1 on morphology and function of DC is measured. Furthermore, to determine whether gal-1 exert inhibitory impact on DC by MAPK pathway, MAPK phosphorylation on DC is examined. Finally, the effect of gal-1 on airway inflammation in acute asthmatic mice model is determined . Investigation benificial effect of MSCs in our study contribute to realizing the development of asthma and providing given guide about early molecular treatment in asthma

已有研究表明移植间充质干细胞（Mesenchymal Stem Cells, MSCs）能减轻哮喘气道炎症及气道高反应性，但MSCs对哮喘免疫调节的机理未明。近期研究提示MSCs能分泌具有免疫抑制作用的半乳凝素-1(galectin-1, gal-1)，而输注gal-3可明显改善哮喘病情。本研究推测MSCs是通过分泌gal-1抑制哮喘树突状细胞( dendritic cell, DC)功能，从而抑制哮喘气道炎症。本研究拟采用体外MSCs与DC直接接触及非直接接触共培养，检测MSCs表达的gal-1对DC形态及功能的影响；进一步检测gal-1对DC中MAPK通路的影响，验证gal-1通过MAPK通路影响DC免疫功能；最后体内检测gal-1对急性哮喘小鼠气道炎症的影响。本研究以MSCs为工具探讨其对哮喘的免疫调节机制，为阐明哮喘的发病机制及早期采取生物靶向治疗提供新思路。