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Inflammation & Allergy - Drug Targets (Discontinued)

Editor-in-Chief

ISSN (Print): 1871-5281
ISSN (Online): 2212-4055

Role of Interleukin-17F in Asthma

Author(s): Mio Kawaguchi, Fumio Kokubu, Junichi Fujita, Shau-Ku Huang and Nobuyuki Hizawa

Volume 8, Issue 5, 2009

Page: [383 - 389] Pages: 7

DOI: 10.2174/1871528110908050383

Price: $65

Abstract

A new family of cytokines, the interleukin (IL)-17 family, has recently been defined, which reveals unique functions and distinct ligand-receptor signaling systems. This family contains six members, IL-17 (also called IL-17A), IL17B, IL-17C, IL-17D, IL-17E (IL-25) and IL-17F. The IL-17F gene was discovered in 2001, and is located on chromosome 6p12. Notably, among this family, IL-17F has been well characterized both in vitro and in vivo, and has been shown to have a pro-inflammatory role in asthma. IL-17F is clearly expressed in the airway of asthmatics and its expression level is correlated with disease severity. Moreover, a coding region variant (H161R) of the IL-17F gene is inversely associated with asthma and encodes an antagonist for the wild-type IL-17F. IL-17F is able to induce several cytokines, chemokines and adhesion molecules in bronchial epithelial cells, vein endothelial cells, fibroblasts and eosinophils. IL-17F utilizes IL-17RA and IL-17RC as its receptors, and activates the MAP kinase related pathway. IL-17F is derived from several cell types such as Th17 cells, mast cells and basophils, and shows a wide tissue expression pattern including lung. Overexpression of IL-17F gene in the airway of mice is associated with airway neutrophilia, the induction of many cytokines, an increase in airway hyperreactivity, and mucus hypersecretion. Hence, IL-17F may have a crucial role in allergic airway inflammation, and have important therapeutic implications in asthma.

Keywords: Asthma, IL-17 family, IL-17A, IL-17F


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