DEXAMETHASONE ACTIVATES EXPRESSION OF THE PDGF-ALPHA RECEPTOR AND INDUCES LUNG FIBROBLAST PROLIFERATION

Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma and in interstitial lung diseases. In attempting to understa nd the mechanisms through which CSs control cell proliferation, we hav e carried out experiments to test the effects of dexamethasone (Dex) o n the growth of lung fibroblasts. Using mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we show that the quiesce nt cells in 1% serum or in serum-free media proliferate significantly in response to the addition of 10(-7) to 10(-9) M Dex. Increases as hi gh as fourfold in cell numbers were recorded for the RLFs after 48 h i n culture. A polyclonal antibody to the AB isoform of human platelet-d erived growth factor (PDGF) blocked the proliferative response. As exp ected, the fibroblasts produced primarily PDGF-alpha chain, and the RL Fs exhibited few PDGF-alpha receptors (PDGF-R alpha), the receptor typ e necessary for binding the AA isoform. Accordingly, we determined tha t Dex upregulated PDGF-R alpha mRNA and protein. Therefore, we can pos tulate that Dex-induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-R alpha.