Interleukin-17 as a Recruitment and Survival Factor for Airway Macrophages in Allergic Airway Inflammation

The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden.
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 3.99). 10/2005; 33(3):248-53. DOI: 10.1165/rcmb.2004-0213OC
Source: PubMed


Recent data indicate that the proinflammatory cytokine, interleukin (IL)-17, stimulates certain effector functions of human macrophages. We evaluated whether IL-17 mediates allergen-induced accumulation of airway macrophages and, if so, whether such an effect relates to the control of macrophage recruitment and survival. BALB/c mice were sensitized and challenged with ovalbumin. Three hours before challenge an anti-mouse IL-17 mAb (a-IL-17) was administered. Sampling was conducted 24 h after the allergen challenge. In vitro chemotaxis assay for blood monocytes and culture of airway macrophages, immunocytochemistry for Fas-antigen, and matrix metalloproteinase-9 (MMP-9) were used to determine the effect of IL-17 on the recruitment, survival, and activity of airway macrophages. A-IL-17 reduced the number of airway neutrophils and macrophages after allergen challenge. In vitro, recombinant IL-17 induced migration of blood monocytes and prolonged survival of airway macrophages. A-IL-17 also increased the expression of Fas-antigen in airway macrophages in vivo. Finally, the expression of MMP-9 by airway neutrophils and macrophages in vivo was downregulated by a-IL-17. This study indicates that endogenous IL-17 mediates the accumulation of macrophages during allergen-induced airway inflammation. IL-17 exerts its effects by acting directly on airway macrophages by promoting their recruitment and survival. Furthermore, IL-17 is involved in controlling the proteolytic activity of macrophages and neutrophils in allergen-induced airway inflammation.

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    • "Interleukin-17, a pro-inflammatory cytokine, inducts neutrophils into the airway via the release of IL-8 from bronchial epithelial cells[12] and arbitrates macrophage accumulation during allergen-induced airway inflammation. It also expends its physiological action by acting directly on airway macrophages and promoting their recruitment and survival[13] and it is possibly associated with the recruitment of eosinophils into the airway.[1415] It has been demonstrated that IL-17 level was increased in bronchoalveolar lavage fluid (BALF), sputum and blood from patients with asthma.[1617] "
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    ABSTRACT: Background:So-Cheong-Ryong-Tang (SCRT), herbal medicine, has been used for the control of respiratory disease in East Asian countries. However, its therapeutic mechanisms, especially an inhibitory effect on inflammatory cell infiltration and airway remodeling in allergic asthma are unclear.Objective:The present study investigated the mechanism of antiasthmatic effects of SCRT in allergic asthma in mice.Materials and Methods:We investigated the influence of SCRT on levels of interleukin-17 (IL-17), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-4, and interferon gamma (IFN-γ) in bronchoalveolar lavage fluid (BALF), ovalbumin (OVA)-specific IgE in serum, and histopathological changes in allergen-induced asthma.Results:So-Cheong-Ryong-Tang decreased levels of IL-17 and GM-CSF in BALF. IL-4, a Th2-driven cytokine, was also decreased by SCRT, but IFN-γ, a Th1-driven cytokine, was not changed. Levels of OVA-specific IgE in serum were also decreased by SCRT. With SCRT treatment, histopathological findings showed reduced tendency of inflammatory cell infiltration, and prevention from airway remodeling such as epithelial hyperplasia.Conclusion:In this study, we firstly demonstrated that regulation of IL-17 and GM-CSF production may be one of the mechanism contributed to a reduction of inflammatory cell infiltration and prevention from airway remodeling.
    Pharmacognosy Magazine 08/2014; 10(39):506. DOI:10.4103/0973-1296.139784 · 1.26 Impact Factor
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    • "IL-17 plays a protective role in host defense against extracellular pathogens and fungus especially at the epithelial and mucosal surface [56]. IL-17 promotes the generation of inflammatory cytokines and chemokines, which attract neutrophils and macrophages to the sites [57, 58]. IL-17-responding targets cells include nonhematopoietic cells including fibroblasts and epithelial cells, as well as macrophages and neutrophils. "
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    ABSTRACT: The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves. However, other non-T cells, particularly APCs, also express receptors for the factors and are capable of responding to them. In this review, we will discuss how APCs, by responding to those cytokines, influence T cell differentiation and adaptive immunity.
    Research Journal of Immunology 07/2014; 2014:750374. DOI:10.1155/2014/750374
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    • "IL-17A has direct chemoattractant effects on macrophages [55], which likely explains the ability of anti-IL-17A to attenuate O3-induced increases in BAL macrophages (Fig. 3A). In contrast, IL-17A induces neutrophil recruitment to the lungs by inducing expression of other neutrophil chemotactic and survival factors. "
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    ABSTRACT: Ozone is an air pollutant that causes pulmonary symptoms. In mice, ozone exposure causes pulmonary injury and increases bronchoalveolar lavage macrophages and neutrophils. We have shown that IL-17A is important in the recruitment of neutrophils after subacute ozone exposure (0.3 ppm for 24-72 h). We hypothesized that γδ T cells are the main producers of IL-17A after subacute ozone. To explore this hypothesis we exposed wildtype mice and mice deficient in γδ T cells (TCRδ-/-) to ozone or room air. Ozone-induced increases in BAL macrophages and neutrophils were attenuated in TCRδ-/- mice. Ozone increased the number of γδ T cells in the lungs and increased pulmonary Il17a mRNA expression and the number of IL-17A+ CD45+ cells in the lungs and these effects were abolished in TCRδ-/- mice. Ozone-induced increases in factors downstream of IL-17A signaling, including G-CSF, IL-6, IP-10 and KC were also decreased in TCRδ-/- versus wildtype mice. Neutralization of IL-17A during ozone exposure in wildtype mice mimicked the effects of γδ T cell deficiency. TNFR2 deficiency and etanercept, a TNFα antagonist, also reduced ozone-induced increases in Il17a mRNA, IL-17A+ CD45+ cells and BAL G-CSF as well as BAL neutrophils. TNFR2 deficient mice also had decreased ozone-induced increases in Ccl20, a chemoattractant for IL-17A+ γδ T cells. Il17a mRNA and IL-17A+ γδ T cells were also lower in obese Cpefat versus lean WT mice exposed to subacute ozone, consistent with the reduced neutrophil recruitment observed in the obese mice. Taken together, our data indicate that pulmonary inflammation induced by subacute ozone requires γδ T cells and TNFα-dependent recruitment of IL-17A+ γδ T cells to the lung.
    PLoS ONE 05/2014; 9(5):e97707. DOI:10.1371/journal.pone.0097707 · 3.23 Impact Factor
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