Immunologic and inflammatory mechanisms that drive asthma progression to remodeling.
Although histologic features of airway remodeling have been well characterized in asthma, the immunologic and inflammatory mechanisms that drive progression of asthma to remodeling are still incompletely understood. Conceptually, airway remodeling may be a result of persistent inflammation and/or aberrant tissue repair mechanisms. It is likely that several immune and inflammatory cell types and mediators are involved in mediating airway remodeling. In addition, different features of airway remodeling are likely mediated by different inflammatory pathways. Several important candidate mediators of remodeling have been identified, including TGF-beta and T(H)2 cytokines (including IL-5 and IL-13), as well as vascular endothelial growth factor, a disintegrin and metalloproteinase 33, and matrix metalloproteinase 9. Mouse models of airway remodeling have provided important insight into potential mechanisms by which TGF-beta activation of the Smad-2/3 signaling pathway may contribute to airway remodeling. Human studies have demonstrated that anti-IL-5 reduces levels of airway eosinophils expressing TGF-beta, as well as levels of airway remodeling as assessed by bronchial biopsies. Further such studies confirming these observations, as well as alternate studies targeting additional individual cell types, cytokines, and mediators, are needed in human subjects with asthma to determine the role of candidate mediators of inflammation on the development and progression of airway remodeling.
Broide
David H
DH
Department of Medicine, University of California San Diego, La Jolla, CA 92093-0635, USA. dbroide@ucsd.edu
D051722:ADAM Proteins / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D051722:ADAM Proteins; C450441:ADAM33 protein, human; D020780:Matrix Metalloproteinase 9