Involvement of a novel cytokine IL-17F in airway remodeling

我们在2001年发现了IL-17F基因，并报道了其在哮喘中的作用。然而，IL-17F在哮喘中的作用尚未完全阐明。虽然吸入性糖皮质激素是长期控制哮喘最有效的药物，但包括吸入性糖皮质激素在内的抗哮喘药物通常对严重哮喘不太有效。为此，治疗重症哮喘是未来世界面临的重大问题。气道重塑与严重哮喘的发病机制密切相关。气道重塑至少部分是由一个复杂的细胞因子网络引起的，包括IL-11和胰岛素样生长因子- i （IGF-I）。为了阐明哮喘气道重塑的发病机制，我们研究了IL-17F对支气管上皮细胞IL-11和IGF-I的诱导作用。IL-17F可通过支气管上皮细胞的Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB信号通路诱导IL-11和IGF-I。因此，IL-17F/IGF-I轴可能参与气道炎症和重塑。因此，IL-17F及其信号通路可能是重度哮喘的有价值的治疗靶点。

We discovered IL-17F gene in 2001, and have reported its function in asthma. However, the role of IL-17F in asthma has not been fully elucidated. Although inhaled corticosteroids are the most potent medicines for long-term control of asthma, anti-asthma medicines including inhaled corticosteroids are generally not so effective for severe asthma. To this end, treating sever asthma is future serious problem in the world. Airway remodeling is deeply involved in the pathogenesis of severe asthma. Airway remodeling is caused by, at least partially, a complicated network of cytokines, including IL-11 and insulin-like growth factor-I (IGF-I). To clarify the pathogenesis of airway remodeling in asthma, we investigated the induction of IL-11 and IGF-I by IL-17F in bronchial epithelial cells. IL-17F is able to induce IL-11 and IGF-I via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. Hence, the IL-17F/IGF-I axis may be involved in airway inflammation and remodeling. Therefore, IL-17F and its signaling pathway may be a valuable therapeutic target for sever asthma.