IL-9决定变应原诱导的肺和慢性气道重塑中肥大细胞的数量
2011/04/15
背景：IL-9是一个多功能细胞因子，在哮喘的病理发生的多方面发挥作用。
目的：早期研究主要集中于IL-9对急性炎症的作用，而该研究对IL-9阻断剂在哮喘慢性变应性炎症中的作用进行了观察。
方法：小鼠长时间暴露于卵白蛋白或尘螨抗原诱导慢性炎症和气道重塑模型。
结果：抗IL-9抗体处理的小鼠气道重塑减轻，同时伴随着成熟肥大细胞数量减少，活性降低，肺内前纤维化介质TGFβ1, VEGF 和FGF-2表达减少。中和IL-9改善气道重塑相关的外周气道肺功能的损害。在哮喘患者肺组织中也发现，肥大细胞是IL-9受体的主要表达细胞，分泌VEGF和FGF-2。
结论：该研究表明IL-9-肥大细胞轴在慢性哮喘中起重要作用，阻断该轴可能可以减轻哮喘患者的慢性炎症并改善肺功能。
（浙江大学附属第二医院呼吸科 王苹莉 摘译）
（Am J Respir Crit Care Med. 2010 Oct 22. [Epub ahead of print]）
IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways.
Kearley J, Erjefalt JS, Andersson C, Benjamin E, Jones CP, Robichaud A, Pegorier S, Brewah Y, Burwell TJ, Bjermer L, Kiener PA, Kolbeck R, Lloyd CM, Coyle AJ, Humbles AA.
Am J Respir Crit Care Med. 2010 Oct 22. [Epub ahead of print]
Abstract
RATIONALE: IL-9 is a pleiotrophic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma.
OBJECTIVES: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models, here we have investigated the effects of IL-9 blockade during chronic allergic inflammation.
METHODS: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling.
MEASUREMENTS AND MAIN RESULTS: We found that IL-9 governs allergen-induced mast cell numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody treated mice were protected from airway remodeling with a concomitant reduction in mature mast cell numbers and activation, in addition to decreased expression of the pro-fibrotic mediators TGFβ1, VEGF and FGF-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified mast cells as the main IL-9 receptor expressing population and found them to be sources of VEGF and FGF-2.
CONCLUSIONS: Our data suggest an important role for an IL-9 - mast cell axis in the pathology associated with chronic asthma, and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma.
目的：早期研究主要集中于IL-9对急性炎症的作用，而该研究对IL-9阻断剂在哮喘慢性变应性炎症中的作用进行了观察。
方法：小鼠长时间暴露于卵白蛋白或尘螨抗原诱导慢性炎症和气道重塑模型。
结果：抗IL-9抗体处理的小鼠气道重塑减轻，同时伴随着成熟肥大细胞数量减少，活性降低，肺内前纤维化介质TGFβ1, VEGF 和FGF-2表达减少。中和IL-9改善气道重塑相关的外周气道肺功能的损害。在哮喘患者肺组织中也发现，肥大细胞是IL-9受体的主要表达细胞，分泌VEGF和FGF-2。
结论：该研究表明IL-9-肥大细胞轴在慢性哮喘中起重要作用，阻断该轴可能可以减轻哮喘患者的慢性炎症并改善肺功能。
（浙江大学附属第二医院呼吸科 王苹莉 摘译）
（Am J Respir Crit Care Med. 2010 Oct 22. [Epub ahead of print]）
IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways.
Kearley J, Erjefalt JS, Andersson C, Benjamin E, Jones CP, Robichaud A, Pegorier S, Brewah Y, Burwell TJ, Bjermer L, Kiener PA, Kolbeck R, Lloyd CM, Coyle AJ, Humbles AA.
Am J Respir Crit Care Med. 2010 Oct 22. [Epub ahead of print]
Abstract
RATIONALE: IL-9 is a pleiotrophic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma.
OBJECTIVES: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models, here we have investigated the effects of IL-9 blockade during chronic allergic inflammation.
METHODS: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling.
MEASUREMENTS AND MAIN RESULTS: We found that IL-9 governs allergen-induced mast cell numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody treated mice were protected from airway remodeling with a concomitant reduction in mature mast cell numbers and activation, in addition to decreased expression of the pro-fibrotic mediators TGFβ1, VEGF and FGF-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified mast cells as the main IL-9 receptor expressing population and found them to be sources of VEGF and FGF-2.
CONCLUSIONS: Our data suggest an important role for an IL-9 - mast cell axis in the pathology associated with chronic asthma, and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma.
上一篇：
消旋沙丁胺醇和左旋沙丁胺醇持续雾化吸入治疗急性哮喘恶化的疗效：随机、双盲、临床试验
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IL-13阻断剂对轻度哮喘患者变应原诱导的气道反应性的影响
