Mediators in asthma
Transforming growth factor-β and its role in asthma

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Abstract

Transforming growth factor-β (TGF-β) is an important fibrogenic and immunomodulatory factor that may play a role in the structural changes observed in the asthmatic airways. In vitro as well as in vivo studies have evidenced a dual role for TGF-β: it can either function as a pro- or anti-inflammatory cytokine on inflammatory cells, participating into the initiation and resultion of inflammatory and immune responses in the airways. TGF-β is also involved in the remodelling of the airway wall, and has in particular been related to the subepithelial fibrosis. TGF-β is produced in the airways by inflammatory cells infiltrated in the bronchial mucosa, as well as by structural cells of the airway wall including fibroblasts, epithelial, endothelial and smooth muscle cells. By releasing TGF-β, these different cell types may then participate into the increased levels of TGF-β observed in bronchoalveolar lavage fluid from asthmatic patients. Taken together, these results suggest that TGF-β may play a role in inflammation in asthma. However, as its role is dual in the modulation of inflammation, further studies are needed to elucidate the precise role of TGF-β in the airways.

Introduction

The transforming growth factor-β (TGF-β) superfamily consists of approximately 30 mammalian cytokines, including different TGF-β isoforms, Müllerian inhibitory substance (MIS), drosophila decapentaplegic gene, activins and inhibins, growth and differentiation factors, bone morphogenetic proteins (BMPs), glial-derived neurotrophic factor and macrophage inhibitory cytokine 1 (MIC-1) [1]. Three closely related isoforms, TGF-β1, -β2 and -β3, have been identified in mammals; TGF β1 is the most prominent and widely studied. TGF-β is expressed throughout the human lung and may regulate cellular processes related to pulmonary physiology and pathology [2]. This potent fibrogenic and immunomodulatory factor is involved in the structural changes that occur in asthmatic airways, including subepithelial fibrosis and the presence of inflammatory infiltrates. This review examines the synthesis and signalling pathways of TGF-β, especially in the airways, and suggests that it plays a role in inflammatory diseases, especially in asthma.

Section snippets

TGF-β expression

TGF-β was first isolated and characterised from platelets [3], but most cell types can produce it [4]: cells from the immune system, including lymphocytes [5], macrophages [6] and mast cells [7], but also structural cells in various tissues, including rat cardiac fibroblasts [8], human umbilical vein endothelial cells [9] and corneal epithelial cells [10].

As shown in vivo by immunohistochemistry and in situ hybridisation, TGF-β is also produced in the airways by various cell types (Fig. 1):

Effects of TGF-β in the airways

The activity of TGF-β on airway structural cells is wide-ranging, related to cell growth, differentiation and migration, and is directly relevant to airway physiology and pathophysiology [4] (Table 2).

Conclusion

Although we would expect mice deficient in TGF-β1 and those overexpressing it to show opposite characteristics in inflammation, they are after all rather similar [197], [198], [200], [201]. This finding confirms what we have reported through this review: TGF-β plays a dual role in the modulation of airway inflammation. As a potent immunomodulator, it appears to orchestrate events vital to the initiation, progression and resolution of immune-mediated inflammatory responses. TGF-β production must

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