Regulation of pulmonary inflammation by mesenchymal cells

Alkhouri, Hatem; Poppinga, W. J.; Tania, Navessa Padma; Ammit, Alaina J.; Schuliga, Michael

doi:10.1016/j.pupt.2014.03.001

Cited by 34 publications

(30 citation statements)

References 170 publications

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“…ABCG2; fibrosis; lung MSC; myofibroblast; pericyte PARENCHYMAL AND VASCULAR REMODELING by mesenchymal-derived cells, such as myofibroblasts, likely share mechanisms that may explain the prevalence of pulmonary hypertension (PH) in pulmonary fibrosis (PF) and interstitial lung disease (ILD) patients (4,28,65,75,77,99). Changes in tissue structure, including fibrosis and microvascular remodeling, result in loss of gas exchange surface area and decreased pulmonary function.…”

Section: Abcg2mentioning

confidence: 99%

ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

Marriott

Baskir

Gaskill

et al. 2014

American Journal of Physiology-Cell Physiology

114

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Section: Abcg2mentioning

confidence: 99%

ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

Marriott

Baskir

Gaskill

et al. 2014

American Journal of Physiology-Cell Physiology

114

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“…Airway remodeling has been seen as a consequence of inflammation, although airway contraction, in the absence of inflammation, can also drive aspects of remodeling (8). Because airway structural changes may support inflammation (9) it is likely that airway inflammation, bronchoconstriction, remodeling, and fixed airflow obstruction interact in a linear, parallel, or combined manner to drive the asthma phenotype.…”

mentioning

confidence: 99%

Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

Naveed

Clements

Jackson

et al. 2017

Am J Respir Crit Care Med

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Rationale: Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma.Objectives: To investigate whether MMP-1 could be activated by mast cells and increase asthma severity.Methods: Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP-1 protein and activity were assessed.Measurements and Main Results: Airway smooth muscle cells generated pro-MMP-1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5-fold (P , 0.05), which was dependent on MMP-1 activation. In asthma, airway pro-MMP-1 was 5.4-fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP-1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP-1 activity increased and was associated with fall in FEV 1 and worsening asthma symptoms.Conclusions: MMP-1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP-1 levels are associated with bronchial hyperresponsiveness, and MMP-1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness.

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“…There is increasing recognition of the potential importance of mesenchymal cells in inflammation (1). Recently, it has been demonstrated that pulmonary fibroblasts and airway smooth muscle cells may participate in the dysregulated inflammatory response seen in COPD (6,31,34).…”

mentioning

confidence: 99%

“…For example, it has been shown that airway fibroblasts of COPD patients express higher levels of IL-6 and chemokine (C-X-C motif) ligand 8 (CXCL8) than airway fibroblasts of controls (34). The inflammatory mediators produced by pulmonary fibroblasts influence the type and quantity of inflammatory cells that infiltrate airway and lung tissue in chronic respiratory disease (1). Taken together, alterations in fibroblast function likely play an important role in COPD.…”

mentioning

confidence: 99%

Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts

Dijk

Menzen

Spanjer

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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COPD is a progressive chronic lung disease characterized by pulmonary inflammation. Several recent studies indicate aberrant expression of WNT ligands and Frizzled receptors in the disease. For example, WNT-5A/B ligand expression was recently found to be increased in lung fibroblasts of COPD patients. However, possible effects of WNT-5A and WNT-5B on inflammation have not been investigated yet. In this study, we assessed the regulation of inflammatory cytokine release in response to WNT-5A/B signaling in human lung fibroblasts. Primary human fetal lung fibroblasts (MRC-5), and primary lung fibroblasts from COPD patients and non-COPD controls were treated with recombinant WNT-5A or WNT-5B to assess IL-6 and CXCL8 cytokine secretion and gene expression levels. Following WNT-5B, and to a lesser extent WNT-5A stimulation, fibroblasts showed increased IL-6 and CXCL8 cytokine secretion and mRNA expression. WNT-5B-mediated IL-6 and CXCL8 release was higher in fibroblasts from COPD patients than in non-COPD controls. In MRC-5 fibroblasts, WNT-5B-induced CXCL8 release was mediated primarily via the Frizzled-2 receptor and TAK1 signaling, whereas canonical β-catenin signaling was not involved. In further support of noncanonical signaling, we showed activation of JNK, p38, and p65 NF-κB by WNT-5B. Furthermore, inhibition of JNK and p38 prevented WNT-5B-induced IL-6 and CXCL8 secretion, whereas IKK inhibition prevented CXCL8 secretion only, indicating distinct pathways for WNT-5B-induced IL-6 and CXCL8 release. WNT-5B induces IL-6 and CXCL8 secretion in pulmonary fibroblasts. In summary, WNT-5B mediates this via Frizzled-2 and TAK1. As WNT-5 signaling is increased in COPD, this WNT-5-induced inflammatory response could represent a therapeutic target.

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Regulation of pulmonary inflammation by mesenchymal cells

Cited by 34 publications

References 170 publications

ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts

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Regulation of pulmonary inflammation by mesenchymal cells

Cited by 34 publications

References 170 publications

ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts

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ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling