Tag: Remodeling

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Where does current and future pediatric asthma treatment stand? Remodeling and inflammation: Bird’s eye view.

Where does current and future pediatric asthma treatment stand? Remodeling and inflammation: Bird’s eye view.

Pediatr Pulmonol. 2016 May 27;

Authors: Yilmaz O, Yuksel H

Abstract
Airway remodeling is the chronic outcome of inflammation in asthma and a point of intervention between pediatric and adult ages. Pediatric asthma has been of great interest in the efforts to find a valuable time to interrupt remodeling. Various experimental and clinical research have assessed the effect of current therapeutic modalities on airway remodeling in asthma and many new agents are being developed with promising results. The heterogeneity in the results of these studies may lie in the heterogeneity of pathogenesis leading to asthma and remodeling; underlying the need for individualized treatment of the unique pathogenetic characteristics of each child’s asthma. The aim of this review is to summarize the evidence about the influence of current and future therapeutic modalities in the concept of inflammation and remodeling in pediatric asthma. Pediatr Pulmonol. 2016; 9999:1-9. © 2016 Wiley Periodicals, Inc.

PMID: 27233079 [PubMed – as supplied by publisher]

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HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.

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HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.

J Immunol. 2016 Jan 29;

Authors: Wang Q, Li H, Yao Y, Lu G, Wang Y, Xia D, Zhou J

Abstract
The airway smooth muscle (ASM) cells’ proliferation, migration, and their progenitor’s migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling.

PMID: 26826248 [PubMed – as supplied by publisher]

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STAT1 Attenuates Murine Allergen-Induced Airway Remodeling and Exacerbation by Carbon Nanotubes.

STAT1 Attenuates Murine Allergen-Induced Airway Remodeling and Exacerbation by Carbon Nanotubes.

Am J Respir Cell Mol Biol. 2015 Mar 25;

Authors: Thompson EA, Sayers BC, Glista-Baker EE, Shipkowski KA, Ihrie MD, Duke KS, Taylor AJ, Bonner JC

Abstract
Asthma is characterized by a T-helper 2 (Th2) phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. STAT1 is a transcription factor that maintains Th1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole body knock-out of the Stat1 gene (Stat1-/-) or wild type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multi-walled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1-/- and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid (BALF), while MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1-/- mice displayed increased IL-13 in BALF 1 day compared to WT mice after treatment with OVA or OVA and MWCNT. At 21 days the lungs of OVA-sensitized Stat1-/- mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1-/- mice at 21 days. These changes corresponded to increased levels of pro-fibrogenic mediators (TGF-?1, TNF-?, OPN) but decreased IL-10 in Stat1-/- mice. Finally, fibroblasts isolated from the lungs of Stat1-/- mice produced significantly more collagen mRNA and protein in response to TGF-?1 compared to WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.

PMID: 25807359 [PubMed – as supplied by publisher]

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Extracellular Matrix Remodeling of the Umbilical Cord and Placenta in Preeclampsia

Conditions:   Alterations of ECM in Umbilical Cord ECM in Preeclampisa;   Alterations of ECM in Placenta in Preeclampisa
Intervention:  
Sponsors:   Zekai Tahir Burak Maternity and Teaching Hospital;   Zekai Tahir Burak Maternity and Teaching Hospital;   turgut ozal university
Recruiting – verified July 2013

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Diffusion lung capacity of carbon monoxide: A novel marker of airways remodeling in asthmatic children?

Diffusion lung capacity of carbon monoxide: A novel marker of airways remodeling in asthmatic children?

Allergy Rhinol (Providence). 2012;3(2):e66-73

Authors: Piacentini GL, Tezza G, Cattazzo E, Kantar A, Ragazzo V, Boner AL, Peroni DG

Abstract
Asthma is universally considered a chronic inflammatory disorder of the airways. Several noninvasive markers, such as exhaled nitric oxide (FeNO) and exhaled breath temperature (PletM), have been proposed to evaluate the degree of airway inflammation and remodeling in asthmatic children. The aim of this study was to evaluate the relationship between diffusion lung capacity of carbon monoxide (DLCO) and these inflammatory markers in asthmatic children. We compared data of FeNO, PletM, and DLCO collected in 35 asthmatic children at admission (T0) and discharge (T1) after a period spent in a dust-mite-free environment (Misurina, Italian Dolomites, 1756 m). PletM showed a reduction from 29.48°C at T0 to 29.13°C at T1 (p = 0.17); DLCO passed from 93 to 102 (p = 0.085). FeNO mean value was 29.7 ppb at admission and 18.9 ppb at discharge (p = 0.014). Eosinophil mean count in induced sputum was 4 at T0 and 2 at T1 (p = 0.004). Spearman standardization coefficient beta was 0.414 between eosinophils and FeNO and -0.278 between eosinophils and DLCO. Pearson’s correlation index between DLCO and PletM was -0.456 (p = 0.019). A negative correlation between DLCO and PletM was found. However, DLCO did not show a significant correlation with FeNO and eosinophils in the airways. Additional studies are needed to clarify the role of DLCO as a potential tool in monitoring childhood asthma.

PMID: 23342292 [PubMed – in process]

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Remodeling Asthma Patients’ Airways – Ivanhoe


MD News (press release)

Remodeling Asthma Patients' Airways
Ivanhoe
(Ivanhoe Newswire) — Asthma is a common chronic respiratory condition characterized clinically by an excessive tendency toward reversible airway narrowing. Scientists believe that the airway narrowing induced by allergen exposure in patients with …
Research revelation could shape future long-term treatment of asthmaHealthCanal.com
Frequent Bronchoconstriction Tied to Airway RemodelingDoctors Lounge

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Allergen-Induced Coexpression of bFGF and TGF-?1 by Macrophages in a Mouse Model of Airway Remodeling: bFGF Induces Macrophage TGF-?1 Expression in vitro.

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Allergen-Induced Coexpression of bFGF and TGF-?1 by Macrophages in a Mouse Model of Airway Remodeling: bFGF Induces Macrophage TGF-?1 Expression in vitro.

Int Arch Allergy Immunol. 2010 Nov 25;155(1):12-22

Authors: Yum HY, Cho JY, Miller M, Broide DH

Background: Basic fibroblast growth factor (bFGF) is a cytokine that is mitogenic for fibroblasts and smooth muscle and may play a role in airway remodeling in asthma. We have used a mouse model of chronic ovalbumin (OVA) allergen-induced airway remodeling to determine whether bFGF and fibroblast growth factor receptor-1 are expressed and regulated by corticosteroids in the airway, as well as to determine whether bFGF mediates expression of another proremodeling cytokine, transforming growth factor (TGF)-?1. Methods: The airway levels and localization of bFGF, FGF receptor-1 and TGF-?1 were determined by ELISA, immunohistology and image analysis in the remodeled airways of chronic OVA-challenged mice treated with either corticosteroids or diluent. In vitro cultures of bone narrow-derived macrophages were used to determine whether bFGF induced TGF-?1 expression. Results: Mice chronically challenged with OVA developed significant airway remodeling that was associated with significantly increased levels of bFGF and TGF-?1. Immunohistochemistry demonstrated significantly increased bFGF and FGF receptor-1 expression by peri- bronchial F4/80+ cells. Double-label immunofluorescence microscopy studies demonstrated that peribronchial macrophages coexpressed bFGF and TGF-?1. In vitro studies demonstrated that incubation of bone marrow-derived macrophages with bFGF induced expression of TGF-?1. Mice treated with corticosteroids and subjected to chronic OVA challenge had significantly reduced levels of bFGF, FGF receptor-1, peribronchial TGF-?1+ cells and airway remodeling. Conclusions: Overall, this study demonstrates that allergen challenge stimulates peribronchial macrophages to coexpress bFGF and TGF-?1 and that bFGF may potentiate macrophage release of TGF-?1 through autocrine and/or paracrine pathways.

PMID: 21109744 [PubMed – as supplied by publisher]

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