Interleukin-26 in Antibacterial Host Defense of Human Lungs


Interleukin-26 in Antibacterial Host Defense of Human Lungs: Effects on Neutrophil Mobilization

Karlhans F Che , Sara Tengvall , Bettina Levänen , Elin Silverpil , Margaretha E Smith , Muhammed Awad , Max Vikström , Lena Palmberg , Ingemar Qvarfordt , Magnus Sköld , and Anders Lindén

Am J Respir Crit Care Med. First published online 07 Oct 2014 as DOI: 10.1164/rccm.201404-0689OC

Abstract
Rationale: The role of the presumed Th17 cytokine interleukin IL-26 in antibacterial host defense of the lungs is not known. Objective: To characterize the role of IL-26 in antibacterial host defense of human lungs. Methods: Intra-bronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage BAL samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and -cytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytokines and phosphorylated STAT1 plus -3 were quantified using ELISA. Gene expression was analyzed by real-time PCR and neutrophil migration was assessed in vitro. Measurements and Main Results: Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages AM displayed gene expression for, contained, and released IL-26. T-helper Th and cytotoxic T Tc cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus -3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells. Conclusion: This study implies that alveolar macrophages produce IL-26 that stimulates receptors on neutrophils and focuses their mobilization towards bacteria and accumulated immune cells in human lungs.KEYWORDS: IL-10, Infection, Inflammation, Macrophage, T cell

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