Prednisolone inhibits PDGF-induced nuclear translocation of NF- B in human pulmonary artery smooth muscle cells

Ogawa A, Firth AL, Yao W, Rubin LJ, Yuan JX. Prednisolone inhibits PDGF-induced nuclear translocation of NFB in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 295: L648–L657, 2008. First published August 15, 2008; doi:10.1152/ajplung.90245.2008.—Pulmonary vascular remodeling, a major cause for the elevated pulmonary vascular resistance in patients with pulmonary arterial hypertension (PAH), is partially due to increased proliferation of pulmonary arterial smooth muscle cells (PASMC) in the media, resulting in vascular wall thickening. Plateletderived growth factor (PDGF) is a potent mitogen that may be involved in the progression of PAH. Blockade of PDGF receptors has been demonstrated to have therapeutic potential for patients with severe pulmonary hypertension. Prednisolone is an immunosuppressant shown to have anti-inflammatory and antiproliferative effects on PASMC. This study was designed to investigate whether PDGF and prednisolone affect human PASMC proliferation by regulating the nuclear translocation of NFB (a transcription factor composed of 2 subunits, p50 and p65). Treatment of human PASMC with PDGF (10 ng/ml) significantly increased nuclear translocation of p50 and p65 subunits. Inhibition of NFB activation or nuclear translocation of p50/p65 significantly attenuated PDGF-induced PASMC proliferation (determined by [H]thymidine incorporation). In the presence of prednisolone (200 M), the PDGF-induced nuclear translocation of p50 and p65 subunits was markedly inhibited (P 0.05 vs. the cells treated with PDGF alone). These results indicate that PDGF-induced nuclear translocation of NFB may play an important role in stimulating PASMC proliferation (and/or enhancing PASMC survival), whereas prednisolone may exert anti-inflammatory and antiproliferative effects on PASMC by inhibiting NFB nuclear translocation.