Epithelium-fibroblast interactions in response to airway inflammation

Dramatic changes to the architecture of the airway walls have been commonly described in the airways of patients with asthma, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Much research has focused on how airway Inflammation drives these structural changes, particularly in t erms of the mechanisms/mediators that are involved and a number of parallel s are observed between the disease phenotypes. For example, the increased d eposition of extracellular matrix (ECM) at local sites In the airway wall i s seen in asthma and all interstitial lung diseases that Involve fibrosis. In addition, increased expression of a number of well characterized cytokin es and growth factors, such as TGF-beta and epidermal growth factor (EGF) h ave been demonstrated in these diseases. However the role of the lesser-kno wn cytokines, including the leukaemia inhibitory factor (LIF) and other mem bers of the IL-6 family of cytokines in the pathogenesis of airway remodell ing and fibrosis is largely unknown. However, the use of genetic manipulati on in vivo and more specific inhibitors/antibodies in vitro has now provide d increasing evidence to support the hypothesis that a complex interaction exists between these cytokines, ECM and integrins in regulating the functio n of both epithelial cells and fibroblasts.