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Effect of Steroids and Long-Acting-Beta Agonist on IL-17F Induced IL-6 and IL-8 Expression

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A7171 - Effect of Steroids and Long-Acting-Beta Agonist on IL-17F Induced IL-6 and IL-8 Expression
Author Block: M. Nakajima1, M. Kawaguchi1, M. Matsuyama1, K. Yoshida1, K. Ota1, J. Fujita1, S. Matsukura2, S. Huang3, Y. Morishima1, Y. Ishii1, H. Satoh1, T. Sakamoto1, N. Hizawa1; 1Dept of Pulmonary Medicine, Univ of Tsukuba, Tsukuba, Japan, 2Respiratory Disease Center, Showa University Northern Yokohama Hospital, Yokohama-shi, Japan, 3Johns Hopkins Asthma and Allergy Ctr, Baltimore, MD, United States.
Background: We and other groups cloned Interleukin (IL)-17F, a member of IL-17 family, in 2001. IL-17F plays a critical role in the pathophysiology of asthma, and airway smooth muscle cells (ASMCs) are important target cells for IL-17F. Our previous study demonstrated that IL-17F induces IL-6 and IL-8 in ASMCs. However, the effect of steroids and long-acting-beta agonist (LABA) on its expression remain to be defined. Objective:We sought to investigate the effect of steroids and LABA on IL-17F induced IL-6 and IL-8 expression and its signaling pathways in ASMCs. Methods:ASMCs were cultured in the presence or absence of IL-17F. The expression of IL-6 and IL-8 were analyzed using real-time PCR and ELISA. The effect of budesonide and formoterol on the expression of IL-6 and IL-8 were investigated. Similary, the involvement of NF-κB and the effect of NF-κB inhibitor BAY 11-7082 on the expression of IL-6 and IL-8 were investigated. Results: Combination with IL-17F and formoterol markedly induced IL-6 and IL-8 expression, when compared with formoterol or IL-17F alone in ASMCs. Budesonide inhibited IL-17F-induced IL-6 and IL-8 expression. Budesonide was also effective in reducing the enhancing effect of formoterol on IL-17F-induced IL-6 and IL-8 expression. IL-17F activated NF-κB. Interestingly, NF-κB inhibitor BAY 11-7082 inhibited IL-17F induced IL-6 expression, but did not inhibit IL-8 expression. Conclusions: These results provided evidence supporting that use of beta-agonists alone exacerbate airway inflammation via enhancing of IL-17F-induced cytokine expression. IL-17F is involved in airway inflammation to induce IL-6 and IL-8 through different signaling pathways in ASMCs.
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