IL-17F is involved in asthma, but its biological function and signaling pathway have not been fully elucidated. IL-11 is clearly expressed in the airway of patients with allergic airway diseases such as asthma, and plays an important role in airway remodeling and inflammation. Therefore, we investigated the expression of IL-11 by IL-17F in bronchial epithelial cells. Bronchial epithelial cells were cultured in the presence or absence of IL-17F, and/or Th2 cytokines (IL-4 and IL-13), or various kinase inhibitors to analyze the expression of IL-11. Next, activation of mitogen- and stress-activated protein kinase (MSK) 1 by IL-17F was investigated. Moreover, the effect of short interfering RNAs (siRNAs) targeting MSK1 and cyclic AMP response element- binding protein (CREB) on IL-17F-induced IL-11 expression was investigated. IL-17F induced IL-11 expression, while the co-stimulation with IL-4 and IL-13 augmented this effect even further. MEK inhibitors, PD98059, U0126, and Raf1 kinase inhibitor I, significantly inhibited IL-11 production; while overexpression of a Raf1 dominant-negative mutant inhibited its expression. IL-17F clearly phosphorylated MSK1, while PD98059 inhibited the phosphorylation of IL-17F-induced MSK1. Both MSK1 inhibitors, Ro-31-8220 and H89, significantly blocked IL-11 expression. Moreover, transfection of the cells with siRNAs targeting MSK1 inhibited activation of CREB, and the siRNAs targeting MSK1 and CREB blocked expression of IL-11. These data suggest that IL-17F may be involved in airway inflammation and remodeling via the induction of IL-11, and RafI-MEK1/2-ERK1/2-MSK1-CREB is identified as a novel signaling pathway participating in this process. Therefore, the IL-17F/IL-11 axis may be a valuable therapeutic target for asthma.