IL-17C Is a Mediator of Respiratory Epithelial Innate Immune Response

• Published in: American journal of respiratory cell and molecular biology Vol. 48; no. 4; pp. 415 - 421
• Main Authors: Pfeifer, Philipp, Voss, Meike, Wonnenberg, Bodo, Hellberg, Jan, Seiler, Frederik, Lepper, Philipp M., Bischoff, Markus, Langer, Frank, Schäfers, Hans-Joachim, Menger, Michael D., Bals, Robert, Beisswenger, Christoph
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.04.2013
• Subjects: Animals; Bronchi - immunology; Bronchi - pathology; Cell Line; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Haemophilus Infections - immunology; Haemophilus Infections - pathology; Haemophilus influenzae - immunology; Humans; Immunity, Innate; Inflammation - immunology; Inflammation - pathology; Interleukin-17 - immunology; Mice; Pseudomonas aeruginosa - immunology; Pseudomonas Infections - immunology; Pseudomonas Infections - pathology; Respiratory Mucosa - immunology; Respiratory Mucosa - pathology; Smoking - immunology; Smoking - pathology; Tobacco Smoke Pollution - adverse effects
• ISSN: 1044-1549; 1535-4989; 1535-4989
• DOI: 10.1165/rcmb.2012-0232OC

The IL-17 family of cytokines consists of at least six members (IL-17A to -F). IL-17 directly activates epithelial cells leading to the expression of inflammatory mediators and antimicrobial factors. Recent studies showed that IL-17C is expressed by epithelial cells. It was the purpose of this study to examine the expression of IL-17 family members in respiratory epithelial cells during bacterial infection. We show that common bacterial pathogens, such as Pseudomonas aeruginosa and Haemophilus influenzae, and ligands of Toll-like receptors 3 and 5 (flagellin, polyI:C) induced the expression and release of IL-17C in cultured human bronchial epithelial cells (HBECs). The expression of IL-17A, -B, -D, or -E was not induced by bacterial stimuli in HBECs. IL-17C enhanced inflammatory responses of respiratory epithelial cells infected with P. aeruginosa. Furthermore, we demonstrate that cigarette smoke suppressed the expression of IL-17C in HBECs in response to bacterial infection and in vivo in the upper airways of mice colonized with H. influenzae. IL-17C could also be detected in bronchial tissue of subjects with infection-related lung diseases. These data show that IL-17C is involved in the innate immune response of respiratory epithelial cells and is suppressed by cigarette smoke.