Effects of corticosteroids on primary mouse lung fibroblasts
Description
Asthma is one of the world's most prevalent airway diseases. A common pathophysiologic finding of asthma is airway subbasement membrane fibrosis which is associated with hyperactive airway contraction. Inhaled corticosteroids have become widely applied to manage asthma due to their safety and efficacy. Many studies have been focused on understanding the molecular mechanisms of action of corticosteroids (CS) and their receptors. There is no evidence as to whether or not CS can influence proliferation of mesenchymal cells and if these cells form the matrix components necessary for the development of airway fibrosis. We have chosen two corticosteroids, Dexamethasone (DEX) and Beclomethasone Dipropionate (BDP), to study their effects on primary mouse lung fibroblast (MLFs) proliferation and growth factor expression My works shows that primary MLFs isolated from C57BL/6 and 129 mice displayed a modest but consistent increase in cell proliferation after CS treatments. DEX and BDP also induced upregulation of PDGF-alpha receptors in MI-Fs, while a generalized decreased expression of TGF-beta, TNF-alpha and alphal procollagen were seen. We can not conclude that CS induced cell proliferation was due to the upregulation of PDGF-alpha receptor since CS treated MLFs did not respond to PDGF-AA and -BB stimulation. Also, CS did not increase the expression of PDGF-C, which is the newly identified ligand for PDGF-alpha receptor Two strains of mice were studied because 129 mice and their lung fibroblasts exhibit reduced firogenic responses. Thus, in all the experiments, 129 and C57 MLFs demonstrated similar patterns of increased or decreased expression of mediators; however, they responded to CS at different concentrations and time points. Generally, 129 MLF expressed less amounts of TGF-beta and PDGF-alpha receptor; additionally, 129 MLF required higher concentrations of CS and longer treatment periods as compared to MLFs from C57 and mice with symptoms of asthma. These studies suggest that CS can influence the pathobiology of interstitial fibroblasts, and further studies to understand this important concept are warranted