New insights into the immunology of chronic obstructive pulmonary disease

Brusselle, Guy; Joos, Guy; Bracke, Ken R.

doi:10.1016/s0140-6736(11)60988-4

Cited by 632 publications

(613 citation statements)

References 104 publications

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“…Cigarette smoke contains several polycyclic aromatic hydrocarbons and dioxins, known to function as AhR ligands. IL-6 and IL-17 have been extensively detected in the lungs of COPD patients (11). Although various therapeutical approaches based on neutralizing Ab against proinflammatory cytokines have been proposed to attenuate airway inflammation in COPD (41,42), the main source and the precise role of IL-6 and IL-17 in this disease remain undefined.…”

Section: Discussionmentioning

confidence: 99%

“…However, these data do not exclude that AhR engagement could directly affect the function of allergy effector cells, namely MCs, beyond T cells. Moreover, increasing evidence suggests alterations in MC populations in patients with chronic obstructive pulmonary disease (COPD), a chronic inflammatory disease mostly associated with cigarette smoking in which innate and adaptive immune cells infiltrate and damage the bronchial mucosa (11). Macrophages, neutrophils, and their proteolytic mediators are involved in the extracellular matrix destruction, whereas CD8 + cytotoxic T cells and Th1 and Th17 cells produce proinflammatory cytokines and promote accumulation of inflammatory cells in the lungs.…”

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confidence: 99%

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The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Sibilano

Frossi

Calvaruso

et al. 2012

The Journal of Immunology

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The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics as well as physiological ligands. These compounds may modulate inflammatory responses and contribute to the rising prevalence of allergic diseases observed in industrialized countries. Mast cells (MCs), located within tissues at the boundary of the external environment, represent a potential target of AhR ligands. In this study, we report that murine and human MCs constitutively express AhR, and its activation by the high-affinity ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation. On the contrary, repeated exposure to FICZ inhibits MC degranulation. Accordingly, histamine release, in an in vivo passive systemic anaphylactic model, is exacerbated by a single dose and is attenuated by repetitive stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a critical player in chronic inflammation and autoimmunity, suggesting a novel pathway for MC activation in the pathogenesis of these diseases. Indeed, histological analysis of patients with chronic obstructive pulmonary disease revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within bronchial lamina propria. Thus, tissue-resident MCs could translate external chemical challenges through AhR by modulating allergic responses and contributing to the generation of inflammation-related diseases.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Sibilano

Frossi

Calvaruso

et al. 2012

The Journal of Immunology

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“…Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoke exposure, and oxidative stress induced by chronic smoke exposure is considered to be a crucial event in the COPD pathogenesis (Brusselle et al 2011). The inflammatory events present in COPD are largely resistant to corticosteroids (Adcock et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

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Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10 −4 M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclearrelated factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10 −8 M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin Vpositive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSEmediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance.

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“…Phagocytically impaired macrophages have been shown to display decreased expression of peroxisome proliferator-activated receptor gamma (PPARy) and efferocytosis-specific bridge molecules, such as growth arrest-specific 6 (GAS6) and milk fat globule-EGF factor 8 protein (MFGE8) 37 . The number of apoptotic cells was shown to increase in COPD because of exposure of lung tissue to toxic chemicals present in cigarette smoke; for example, and their accumulation was exacerbated by the simultaneous smoke-induced impairment of the phagocytic ability of alveolar macrophages 38 . Apoptotic cells exhibit surface changes that distinguish them from viable cells, and these changes were recognized by efferocytic receptors including CD36 molecule (CD36), CD14 molecule (CD14), and Stabilin-1/2 (STAB1:STAB2) 39 .…”

Section: Exemplary Outcomes Of the Three-phase Copd Network Building mentioning

confidence: 99%

Enhancement of COPD biological networks using a web-based collaboration interface

et al. 2015

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The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks.

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New insights into the immunology of chronic obstructive pulmonary disease

Cited by 632 publications

References 104 publications

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Enhancement of COPD biological networks using a web-based collaboration interface

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