The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers

Fru, Karlhans; Tufvesson, Ellen; Tengvall, Sara; Lappi‐Blanco, Elisa; Kaarteenaho, Riitta; Levänen, Bettina; Ekberg, Marie; Brauner, Annelie; Wheelock, Åsa M.; Bjermer, Leif; Sköld, C. Magnus; Lindén, Anders

doi:10.1042/cs20180057

Cited by 22 publications

(30 citation statements)

References 47 publications

(79 reference statements)

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“…Different studies have reported that IL-26 activates innate (27) and adaptive lymphoid cells (28) as well as myeloid cells (29) and plasmacytoid dendritic cells (pDC) (18). However, with the exception of alveolar macrophages (25) and non-stimulated neutrophils (26, 30), immune cells do not express IL-20R1, suggesting the existence of alternative IL-26-signaling pathway(s) in the activation of IL-20R1-negative cells.…”

Section: The Il-26 Protein and Signaling Elementsmentioning

confidence: 99%

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

et al. 2019

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Interleukin 26 (IL-26) is the most recently identified member of the IL-20 cytokine subfamily, and is a novel mediator of inflammation overexpressed in activated or transformed T cells. Novel properties have recently been assigned to IL-26, owing to its non-conventional cationic, and amphipathic features. IL-26 binds to DNA released from damaged cells and, as a carrier molecule for extracellular DNA, links DNA to inflammation. This observation suggests that IL-26 may act both as a driver and an effector of inflammation, leading to the establishment of a deleterious amplification loop and, ultimately, sustained inflammation. Thus, IL-26 emerges as an important mediator in local immunity/inflammation. The dysregulated expression and extracellular DNA carrier capacity of IL-26 may have profound consequences for the chronicity of inflammation. IL-26 also exhibits direct antimicrobial properties. This review summarizes recent advances on the biology of IL-26 and discusses its roles as a novel kinocidin.

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Section: The Il-26 Protein and Signaling Elementsmentioning

confidence: 99%

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

et al. 2019

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“…18 Moreover, IL-26 enhances the chemotactic response of human neutrophils to bacterial and inflammatory stimuli. 12 In this way, Che et al 19 found increased extracellular IL-26 protein in the airways of long-term smokers in vivo. Recombinant human IL-26 increased gene expression of NF-κB and pro-inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 90%

“…Recombinant human IL-26 increased gene expression of NF-κB and pro-inflammatory cytokines. 19 Innate lymphoid cells (ILCs) are part of the innate immune system. 20 ILC3s, the most implicated in asthma can play a role in the recruitment of neutrophils to the lung via the cytokine IL-17A eventually leading to neutrophilic inflammation.…”

Section: Introductionmentioning

confidence: 99%

<p>Sputum IL-26 Is Overexpressed in Severe Asthma and Induces Proinflammatory Cytokine Production and Th17 Cell Generation: A Case–Control Study of Women</p>

Louhaichi¹,

Mlika²,

Hamdi³

et al. 2020

JAA

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Objective: Asthma inflammation is a complex pathway involving numerous mediators. Interleukin-26 (IL-26), a member of the IL-10 cytokine family, is abundant in human airways and induces the production of proinflammatory cytokines. Our aim was to investigate the possible role of IL-26 in severe asthma. We analysed the expression of IL-26 in severe asthma both in peripheral blood and induced sputum. Patients and Methods: A total of 50 adult women with severe asthma were recruited and compared to 30 healthy controls (HC). Serum and sputum fluid (SF) levels of IL-26 and IL-17 were defined by ELISA. IL-26 mRNA expression and IL-26 protein were analysed using RT-PCR and Western blot. In vitro, we studied the effect of recombinant IL-26 (rIL-26) and SF-IL-26 on cultured CD4 + T cells and monocytes, comparing patients and controls. Results: Concentrations of IL-26 are higher in serum and induced sputum of asthmatic patients than in HC. Moreover, IL-26 protein and mRNA expression were significantly elevated in asthma sputum cells compared to PBMCs. We observed a positive correlation between body mass index (BMI) and sputum fluid IL-26, while the correlation between IL-26 and lung function tests (FEV1% and FEV1/FVC ratio) was negative. IL-17A was highly expressed in SF and correlated positively with IL-26. In patients' sputum IL-26 and IL-17A were significantly associated with neutrophils. Stimulation of cultured CD4 + T cells with monocytes by recombinant IL-26 promoted the generation of RORγt + Th17 + cells inducing the production of IL-17A, IL-1β, IL-6 and TNF-α cytokines. IL-26 expressed in SF was biologically active and induced IL-17 secretion in the presence of IL-1β and IL-6 cytokines. Conclusion: These findings show that IL-26 is highly produced in asthmatic sputum, induces pro-inflammatory cytokine secretion by monocytes/macrophages, and favours Th17 cell generation. IL-26 thereby appears as a novel pro-inflammatory cytokine, produced locally in the airways that may constitute a promising target to treat asthma inflammatory process.

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“…Another candidate for neutrophil-targeted therapy may be IL-26, which is a neutrophil mobilizing cytokine that is increased in BALF of COPD patients and long term smokers [136]. In addition, an alternative treatment strategy may be the use of AZD7986, a competitive and reversible inhibitor of dipeptidyl peptidase 1 (DPP1), which was shown to inhibit whole blood NE activity in healthy volunteers after once-daily dosing for 21-28 days with no serious side effects [137].…”

Section: Granulocyte-targeted Therapies For Copdmentioning

confidence: 99%

Granulocyte-targeted therapies for airway diseases

Tavares

Peh

Tan

et al. 2020

Pharmacological Research

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The average respiration rate for an adult is 12-20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory diseases, which includes asthma, chronic obstructive pulmonary disease (COPD) and acute lower respiratory tract infections (LTRI), are a major cause of death worldwide. Although asthma, COPD and LTRI are distinctly different diseases with separate mechanisms of disease progression, they do share a common featureairway inflammation with intense recruitment and activation of granulocytes and mast cells. Neutrophils, eosinophils, basophils, and mast cells are crucial players in host defense against pathogens and maintenance of lung homeostasis. Upon contact with harmful particles, part of the pulmonary defense mechanism is to recruit these cells into the airways. Despite their protective nature, overactivation or accumulation of granulocytes and mast cells in the lungs results in unwanted chronic airway inflammation and damage. As such, understanding the bright and the dark side of these leukocytes in lung physiology paves the way for the development of therapies targeting this important mechanism of disease. Here we discuss the role of granulocytes in respiratory diseases and summarize therapeutic strategies focused on granulocyte recruitment and activation in the lungs.

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The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers

Cited by 22 publications

References 47 publications

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

<p>Sputum IL-26 Is Overexpressed in Severe Asthma and Induces Proinflammatory Cytokine Production and Th17 Cell Generation: A Case–Control Study of Women</p>

Granulocyte-targeted therapies for airway diseases

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