Che, K., Tufvesson, E., Tengvall, S., Lappi-Blanco, E., Kaarteenaho, R., Levänen, B., Ekberg, M., Brauner, A., Wheelock, Å.,, Bjermer, L., Sköld, C., Lindén, A. (2018) The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers. Clinical Science, 132 (9), 959-983. doi:10.1042/CS20180057
The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
|Author:||Che, Karlhans Fru1; Tufvesson, Ellen2; Tengvall, Sara3;|
1Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm SE-171 77, Sweden
2Respiratory Medicine and Allergology, Department of Clinical Sciences, Lund University, Lund, Sweden
3Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SE-405 30, Sweden
4Department of Pathology, Center for Cancer Research and Translational Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland
5Respiratory Medicine, Research Unit of Internal Medicine, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
6Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska University Hospital and Karolinska Institutet, Stockholm SE-171 76, Sweden
7Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm SE-171 76, Sweden
8Lung Allergy Clinic, Karolinska University Hospital, New Karolinska Solna, Stockholm SE-171 76, Sweden
|Online Access:||PDF Full Text (PDF, 1.3 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019062021536
|Publish Date:|| 2019-06-20
Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor κ B (NF-κB); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-κB and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
|Pages:||959 - 983|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
This work was supported by the Foundation Olle Bohlin (to A.L.); the federal funding through Karolinska Institutet (to A.L.); King Gustaf V’s and Queen Victoria’s Freemason Research Foundation (to A.L.); the Stockholm County Council [grant number ALF No. 20140309 (to A.L.)]; the Swedish Heart-Lung Foundation [grant number 20150303 (to A.L.)]; the Swedish Research Council [grant number 2016-01653 (to A.L.)]; the Västra Götaland Region [grant number LUA No. 141851 (to A.L.)]; the Swedish Heart-Lung Foundation [grant number 20130293 (to C.M.S.)]; the King Oscar II Jubilee Foundation (to C.M.S.); the Mats Kleberg Foundation (to C.M.S.); the King Gustaf V’s and Queen Victoria’s Freemasons’ Foundation (to C.M.S.); the Hesselmans Foundation (to C.M.S.); the Swedish Governmental Agency for Innovation Systems (VINNOVA) (to C.M.S.); the Swedish Foundation for Strategic Research (SSF) (to C.M.S.); the European Union (EU) Fp6 Marie Curie International Reintegration Grant (IRF) (to C.M.S.); the Swedish Research Council (VR) (to C.M.S.), the Stockholm County Council [grant number ALF No. 20150061 (to C.M.S.)]; the Karolinska Institutet (to C.M.S.); the Swedish Heart-Lung Foundation [grant numbers HLF20160427, HLF20120801, HLF20130486 (to Å.M.W.)]; the Swedish Foundation for Strategic Research [grant number A514 06/0123 (to Å.M.W.)]; the European Union (EU) Fp6 Marie Curie International Reintegration Grant [grant number IRG_046516 (to Å.M.W.)]; the Swedish Research Council [grant number K2014-58X-22502-01-5 (to Å.M.W.)]; the Heart-Lung Fund [grant number 20080462 (to E.T.)]; the Evy and Gunnar Sandberg’s Foundation [grant number 2008/3623 (to E.T.)]; the Royal Physiographic Society in Lund [grant numbers 32779, 34549, 36139 (to E.T.)]; the Region Skåne Research Funds (to E.T.); and the Regional Funding from Skåne County Council [grant number ALF No. 2014/354 (to E.T.)].
© 2018 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).