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

Aiko Ogawa, Amy L. Firth, Weijuan Yao, Lewis J. Rubin, Jason X.J. Yuan

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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. Platelet-derived 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 NF-κB (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 NF-κB activation or nuclear translocation of p50/p65 significantly attenuated PDGF-induced PASMC proliferation (determined by [ 3H]thymidine incorporation). In the presence of prednisolone (200 μM), 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 NF-κB 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 NF-κB nuclear translocation.

Original languageEnglish (US)
Pages (from-to)L648-L657
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Keywords

  • Immunosuppressant
  • Proliferation
  • Pulmonary arterial hypertension
  • Therapy

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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