Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo

Hoshino, Hiroshi; Laan, Martti; Sjöstrand, Margareta; Lötvall, Jan; Skoogh, Bengt-Eric; Lindén, Anders

doi:10.1016/s0091-6749(00)90189-1

Cited by 125 publications

(109 citation statements)

References 27 publications

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“…The corresponding percentages for 24 h after endotoxin exposure were 5 (2-8) in BAL samples from the vehicle-exposed segments and 5 (3)(4)(5)(6)(7)(8) in BAL samples from the endotoxin-exposed segments. …”

Section: Cd4mentioning

confidence: 97%

Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin

Glader¹,

Smith²,

Malmhäll³

et al. 2010

European Respiratory Journal

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Previous studies on mouse models have indicated that interleukin (IL)-17 and IL-17-producing T-helper (Th) cells are important for pulmonary host defence against Gram-negative bacteria. Human correlates to these findings have not yet been demonstrated. The aim of the present study was to determine whether or not IL-17-producing Th cells are present and whether IL-17 and other Th17-associated cytokines are involved in the immunological response to endotoxin in human airways.Segmental exposure to endotoxin and contralateral exposure to vehicle were performed in the lungs of healthy volunteers, with subsequent bronchoalveolar lavage 12 or 24 h after exposure to study local changes in cytokines and inflammatory cells.Endotoxin exposure increased concentrations of IL-17, IL-22 and their downstream effector molecules, human b-defensin-2 and IL-8/CXC chemokine ligand 8, in bronchoalveolar lavage fluid. Th cells with the capacity to produce IL-17 were found among the bronchoalveolar lavage cells, and expression of IL-17 mRNA correlated with expression of the transcription factor, retinoic-acidreceptor-related orphan receptor C variant 2. Moreover, endotoxin increased the numbers of neutrophils, macrophages and IL-17-producing T-cells, as well as the concentration of the Th17-regulating cytokines, IL-21 and IL-23.In conclusion, IL-17-producing Th cells are present, and IL-17, as well as other Th17-associated cytokines, is involved in the immunological response to endotoxin in human airways.

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Section: Cd4mentioning

confidence: 97%

Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin

Glader¹,

Smith²,

Malmhäll³

et al. 2010

European Respiratory Journal

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“…This hypothesis was initially based merely on plain experimental studies that documented the neutrophil mobilising potential of IL-17A protein in animal airway models in vivo plus models of human bronchial epithelial and venous endothelial cells in vitro [15][16][17]. In essence, the results of these early experimental studies indicated that IL-17A recruits and accumulates neutrophils indirectly into the airways by inducing the transcription and release of neutrophil mobilising cytokines from structural airway cells ( fig.…”

Section: Original Hypothesis On Neutrophil Accumulationmentioning

confidence: 99%

“…1). These early studies and the subsequent studies on ''pro-inflammatory effects'' of IL-17A demonstrated that the IL-17-induced accumulation of neutrophils is also associated with an increase in proteolytic enzymes, including neutrophil elastase and matrix metalloproteinase-9 [17,18]. The initial evidence for the actual involvement of IL-17A in patients with asthma was published several years later by MOLET et al [19] and the observations in patients thereafter rapidly obtained support in two subsequent studies [20,21].…”

Section: Original Hypothesis On Neutrophil Accumulationmentioning

confidence: 99%

Interleukin-17 cytokine signalling in patients with asthma

Lindén

Dahlén

2014

Eur Respir J

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Asthma remains a global health problem and, therefore, more effective pharmacotherapy is needed. This is particularly true for chronic and severe asthma. In these clinical phenotypes, chronic inflammation involving neutrophils is likely to play a pathogenic role, making it interesting to target cytokine signalling involved in the accumulation of neutrophils. Therefore, it is of interest that the archetype T-helper 17 cell cytokine interleukin (IL)-17A, perhaps also IL-17F, controls neutrophil accumulation, mucus secretion, macrophage mobilisation and smooth muscle reactivity in various experimental airway models. However, much less is known about the involvement of signalling via IL-17 cytokines in humans with asthma. Existing evidence suggests that these cytokines are released from several types of immune cells in asthma and, for IL-17A, there is a local increase associated with disease severity, with the mobilisation of neutrophils and smooth muscle cells locally in the airways. Even though the causative role of IL-17 cytokines remains unclear, there is potential for clinical utility in targeting IL-17A specifically in patients with moderate-to-severe asthma and high reversibility. There is a need for new and well-powered clinical investigations of signalling via IL-17 cytokines in this clinical phenotype. @ERSpublications There is potential utility for drugs targeting IL-17 cytokine signalling in a sub-group of patients with asthma

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“…IL-17 (also known as IL-17A) is a T cell-derived proinflammatory cytokine, which is involved in accumulation and activation of neutrophils (7,8). IL-17 induces mobilization of neutrophils indirectly via production of several cytokines, CSFs, and C-X-C chemokines (9).…”

mentioning

confidence: 99%

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

Shibata

Yamada

Hara

et al. 2007

The Journal of Immunology

440

410

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Neutrophils infiltrate the site of infection and play critical roles in host defense, especially against extracellular bacteria. In the present study, we found a rapid and transient production of IL-17 after i.p. infection with Escherichia coli, preceding the influx of neutrophils. Neutralization of IL-17 resulted in a reduced infiltration of neutrophils and an impaired bacterial clearance. Ex vivo intracellular cytokine flow cytometric analysis revealed that γδ T cell population was the major source of IL-17. Mice depleted of γδ T cells by mAb treatment or mice genetically lacking Vδ1 showed diminished IL-17 production and reduced neutrophil infiltration after E. coli infection, indicating an importance of Vδ1+ γδ T cells as the source of IL-17. It was further revealed that γδ T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23, which was induced rapidly after E. coli infection in a TLR4 signaling-dependent manner. Thus, although γδ T cells are generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses, our study demonstrated a novel role of γδ T cells as a first line of host defense controlling neutrophil-mediated innate immune responses.

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Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo

Cited by 125 publications

References 27 publications

Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin

Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin

Interleukin-17 cytokine signalling in patients with asthma

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

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