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TGF-beta Isoform Specific Regulation of Airway Inflammation and Remodelling in a Murine Model of Asthma

Bottoms, SE; Howell, JE; Reinhardt, AK; Evans, IC; McAnulty, RJ; (2010) TGF-beta Isoform Specific Regulation of Airway Inflammation and Remodelling in a Murine Model of Asthma. PLOS ONE , 5 (3) , Article e9674. 10.1371/journal.pone.0009674. Green open access

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Abstract

The TGF-beta family of mediators are thought to play important roles in the regulation of inflammation and airway remodelling in asthma. All three mammalian isoforms of TGF-beta, TGF-beta(1-3), are expressed in the airways and TGF-beta(1) and -beta(2) are increased in asthma. However, there is little information on the specific roles of individual TGF-beta isoforms. In this study we assess the roles of TGF-beta(1) and TGF-beta(2) in the regulation of allergen-induced airway inflammation and remodelling associated with asthma, using a validated murine model of ovalbumin sensitization and challenge, and isoform specific TGF-beta neutralising antibodies. Antibodies to both isoforms inhibited TGF-beta mediated Smad signalling. Anti-TGF-beta(1) and anti-TGF-beta(2) inhibited ovalbumin-induced sub-epithelial collagen deposition but anti-TGF-beta(1) also specifically regulated airway and fibroblast decorin deposition by TGF-beta(1). Neither antibody affected the allergen-induced increase in sub-epithelial fibroblast-like cells. Anti-TGF-beta(1) also specifically inhibited ovalbumin-induced increases in monocyte/ macrophage recruitment. Whereas, both TGF-beta(1) and TGF-beta(2) were involved in regulating allergen-induced increases in eosinophil and lymphocyte numbers. These data show that TGF-beta(1) and TGF-beta(2) exhibit a combination of specific and shared roles in the regulation of allergen-induced airway inflammation and remodelling. They also provide evidence in support of the potential for therapeutic regulation of specific subsets of cells and extracellular matrix proteins associated with inflammation and remodelling in airway diseases such as asthma and COPD, as well as other fibroproliferative diseases.

Type: Article
Title: TGF-beta Isoform Specific Regulation of Airway Inflammation and Remodelling in a Murine Model of Asthma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0009674
Publisher version: http://dx.doi.org/10.1371/journal.pone.0009674
Language: English
Additional information: © 2010 Bottoms et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by grants from Asthma UK www.asthma.org.uk (grant number 04/017) and the Wellcome Trust www.wellcome.ac.uk (grant number 060109). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: GROWTH-FACTOR-BETA, BRONCHOALVEOLAR LAVAGE FLUID, SUBEPITHELIAL FIBROSIS, BRONCHIAL-ASTHMA, GENE-EXPRESSION, MESSENGER-RNA, PROTEOGLYCAN DEPOSITION, ALVEOLAR MACROPHAGES, TARGETED DISRUPTION, ALLERGEN CHALLENGE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/124035
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