University of Oulu

Che, K. F., Kaarteenaho, R., Lappi-Blanco, E., Levänen, B., Sun, J., Wheelock, Å., … Lindén, A. (2017). Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines. Molecular Medicine, 23(1), 247–257.

Interleukin-26 production in human primary bronchial epithelial cells in response to viral stimulation : modulation by Th17 cytokines

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Author: Che, Karlhans Fru1; Kaarteenaho, Riitta2; Lappi-Blanco, Elisa3;
Organizations: 1Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
2Unit of Medicine and Clinical Research, Pulmonary Division, University of Eastern Finland and Center of Medicine and Clinical Research, Division of Respiratory Medicine, Kuopio University Hospital, Kuopio, Finland
3Department of Pathology, Center for Cancer Research and Translational Medicine, University of Oulu, Oulu, Finland
4Respiratory Medicine Unit. Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
5Lung Allergy Clinic, Karolinska University Hospital Solna, Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.5 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2019-09-16


Interleukin (IL)-26 is abundant in human airways and this cytokine is involved in the local immune response to a bacterial stimulus in vivo. Specifically, local exposure to the toll-like receptor (TLR) 4 agonist endotoxin does increase IL-26 in human airways and this cytokine potentiates chemotactic responses in human neutrophils. In addition to T-helper (Th) 17 cells, alveolar macrophages can produce IL-26, but it remains unknown whether this cytokine can also be produced in the airway mucosa per se in response to a viral stimulus. Here, we evaluated whether this is the case using primary bronchial epithelial cells from the airway epithelium in vitro and explored the signaling mechanisms involved, including the modulatory effects of additional Th17 cytokines. Finally, we assessed IL-26 and its archetype signaling responses in healthy human airways in vivo. We found increased transcription and release of IL-26 protein after stimulation with the viral-related double stranded (ds) RNA polyinosinic-polycytidylic acid (poly-IC) and showed that this IL-26 release involved mitogen-activated protein (MAP) kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The release of IL-26 in response to a viral stimulus was modulated by additional Th17 cytokines. Moreover, there was transcription of IL26 mRNA and expression of the protein in epithelial cells of bronchial brush and tissue biopsies respectively after harvest in vivo. In addition, the extracellular IL-26 protein concentrations in bronchoalveolar lavage (BAL) samples did correlate with increased epithelial cell transcription of an archetype intracellular signaling molecule downstream of the IL-26-receptor complex, STAT1, in the bronchial brush biopsies. Thus, our study suggests that viral stimulation causes the production of IL-26 in lining epithelial cells of human airways, structural cells that constitute a critical immune barrier and that this production is modulated by Th17 cytokines.

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Series: Molecular medicine
ISSN: 1076-1551
ISSN-E: 1528-3658
ISSN-L: 1076-1551
Volume: 23
Pages: 247 - 257
DOI: 10.2119/molmed.2016.00064
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: Project funding was obtained from the Swedish Heart-Lung Foundation (No. 20150303), the Swedish Research Council (No. 2016-01653), King Gustav V’s and Queen Victoria’s Freemason Research Foundation (ALF No. 20140309). In addition, federal funding was obtained from Karolinska Institutet and, through the Regional ALF Agreement. Project funding was also obtained from Foundation of the Finnish Anti-Tuberculosis Association.
Copyright information: © The Authors 2017. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it.