TGF-beta: its role in asthma and therapeutic potential

Asthma is a chronic disease of the airways affecting around 10% of the population. The majority of cases are well controlled with current therapies, however in approximately 20% of severe asthmatics the available therapeutic strategies are inadequate. Structural changes in the asthmatic airway, including an increase in smooth muscle mass and an increased deposition of extracellular matrix proteins, which correlate with airway hyperresponsivenes, reduced lung function and an increase in fibroblast/myofibroblast numbers, are not specifically targetted by current therapeutic agents and therefore represent an area of unmet need. The mechanisms involved in the development of airway remodelling are incompletely understood but are thought to involve one or more isoforms of transforming growth factor-beta (TGF-beta). The TGF-betas are pleiotropic mediators which have important roles in the regulation of inflammation, cell growth, differentiation and wound healing. All three mammalian isoforms of TGF-beta are present in the airways and at least TGF-beta1 and TGF-beta2 have been shown to be increased in asthmatic airways and cells, together with evidence of increased TGF-beta signalling. In addition, evidence from animal models suggests that airway remodelling may be prevented or reversed using agents which target TGF-beta. Therefore modulation of TGF-betas or their activity represent a potential therapeutic target for asthma. This review focuses on the current knowledge of TGF-beta1-3, their their role in normal and asthmatic airways, as well as the potential for modulating the TGF-betas and their effects as a therapeutic approach to asthma.