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Am J Physiol Lung Cell Mol Physiol. 2016 Nov 1;311(5):L1015-L1022. doi: 10.1152/ajplung.00158.2016. Epub 2016 Sep 30.

IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acute Pseudomonas aeruginosa pneumonia.

Author information

1
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
2
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany; and.
3
Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany.
4
Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, Saarland University, Saarbrücken, Germany.
5
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany; christoph.beisswenger@uks.eu.

Abstract

Lung epithelial cells are suggested to promote pathogen-induced pulmonary inflammation by the release of chemokines, resulting in enhanced recruitment of circulating leukocytes. Recent studies have shown that the interleukin-17C (IL-17C) regulates innate immune functions of epithelial cells in an autocrine manner. The aim of this study was to investigate the contribution of IL-17C to pulmonary inflammation in a mouse model of acute Pseudomonas aeruginosa pneumonia. Infection with P. aeruginosa resulted in an increased expression of IL-17C in lung tissue of wild-type mice. Numbers of neutrophils and the expression of the neutrophil-recruiting chemokines keratinocyte-derived chemokine and macrophage inflammatory protein 2 were significantly decreased in lungs of IL-17C-deficient (IL-17C-/-) mice infected with P. aeruginosa at 24 h. Systemic concentrations of interleukin-6 (IL-6) were significantly decreased in infected IL-17C-/- mice at 24 h and the survival of IL-17C-/- mice was significantly increased at 48 h. The expression of IL-17C was reduced in infected mice deficient for interleukin-17A (IL-17A), whereas pulmonary concentrations of IL-17A were not affected by the deficiency for IL-17C. Stimulation of primary alveolar epithelial cells with IL-17A resulted in a significantly increased expression of IL-17C in vitro. Our data suggest that IL-17A-mediated expression of epithelial IL-17C amplifies the release of chemokines by epithelial cells and thereby contributes to the recruitment of neutrophils and systemic inflammation during acute P. aeruginosa pneumonia.

KEYWORDS:

IL-17A; IL-17C; P. aeruginosa; inflammation; pathology; pneumonia; sepsis

PMID:
27694471
DOI:
10.1152/ajplung.00158.2016
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