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

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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.