Controversy surrounding the increased expression of TGF beta 1 in asthma.
Asthma is a waxing and waning disease that leads to structural changes in the airways, such as subepithelial fibrosis, increased mass of airway smooth muscle and epithelial metaplasia. Such a remodeling of the airways further amplifies asthma symptoms, but its etiology is unknown. Transforming growth factor beta1 is a pleiotropic cytokine involved in many fibrotic, oncologic and immunologic diseases and is believed to play an essential role in airway remodeling that occurs in asthmatic patients. Since it is secreted in an inactive form, the overall activity of this cytokine is not exclusively determined by its level of expression, but also by extensive and complex post-translational mechanisms, which are all important in modulating the magnitude of the TGFbeta1 response. Even if TGFbeta1 upregulation in asthma is considered as a dogma by certain investigators in the field, the overall picture of the published literature is not that clear and the cellular origin of this cytokine in the airways of asthmatics is still a contemporaneous debate. On the other hand, it is becoming clear that TGFbeta1 signaling is increased in the lungs of asthmatics, which testifies the increased activity of this cytokine in asthma pathogenesis. The current work is an impartial and exhaustive compilation of the reported papers regarding the expression of TGFbeta1 in human asthmatics. For the sake of comparison, several studies performed in animal models of the disease are also included. Inconsistencies observed in human studies are discussed and conclusions as well as trends from the current state of the litterature on the matter are proposed. Finally, the different points of regulation that can affect the amplitude of the TGFbeta1 response are briefly revised and the possibility that TGFbeta1 is dysregulated at another level in asthma, rather than simply in its expression, is highlighted.
Bossé
Ynuk
Y
Immunology Division, Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. ybosse@mrl.ubc.ca
Rola-Pleszczynski
Marek
M
D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
D053773:Transforming Growth Factor beta1