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Molecular Medicine

, Volume 23, Issue 1, pp 247–257 | Cite as

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

  • Karlhans Fru Che
  • Riitta Kaarteenaho
  • Elisa Lappi-Blanco
  • Bettina Levänen
  • Jitong Sun
  • Åsa Wheelock
  • Lena Palmberg
  • C. Magnus Sköld
  • Anders Lindén
Research Article

Abstract

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.

Notes

Acknowledgments

We thank Jie Ji, M.Sc., Institute of Environmental Medicine, Karolinska Institutet, for assisting with primary bronchial epithelial cells as well as Max Vikström, Unit for Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, for assisting with the statistics. We also thank Emma Åkerlund, Unit for Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet for assistance with the western blot assay.

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. No funding was obtained from the tobacco industry.

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Authors and Affiliations

  • Karlhans Fru Che
    • 1
  • Riitta Kaarteenaho
    • 2
  • Elisa Lappi-Blanco
    • 3
  • Bettina Levänen
    • 1
  • Jitong Sun
    • 1
  • Åsa Wheelock
    • 4
  • Lena Palmberg
    • 1
  • C. Magnus Sköld
    • 4
    • 5
  • Anders Lindén
    • 1
    • 5
  1. 1.Unit for Lung and Airway Research, Institute of Environmental MedicineKarolinska InstitutetStockholmSweden
  2. 2.Unit of Medicine and Clinical Research, Pulmonary Division, University of Eastern Finland and Center of Medicine and Clinical Research, Division of Respiratory MedicineKuopio University HospitalKuopioFinland
  3. 3.Department of Pathology, Center for Cancer Research and Translational MedicineUniversity of OuluOuluFinland
  4. 4.Respiratory Medicine Unit. Center for Molecular Medicine, Department of Medicine SolnaKarolinska InstitutetStockholmSweden
  5. 5.Lung Allergy ClinicKarolinska University Hospital SolnaStockholmSweden

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