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

American Journal of Physiology. Lung Cellular and Molecular Physiology
Aiko OgawaJason X-J Yuan

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-kappaB (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-kappaB activation or nuclear translocation of p50/p65 significantly attenuated PDGF-induced PASMC proliferation (determined by [(3)H]thymidine incorporation). In the presence of prednisolone (200 microM), the PDGF-induced nuclear translocation of p50 and p65...Continue Reading

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Citations

Jan 17, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jamie K PatelAlan J Knox
Feb 9, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Amy L FirthJason X-J Yuan
Jan 5, 2011·American Journal of Respiratory and Critical Care Medicine·Aiko OgawaHiroshi Ito
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Jun 9, 2020·Frontiers in Bioengineering and Biotechnology·Chiharu MoriiAiko Ogawa
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Mar 7, 2021·International Journal of Molecular Sciences·Aleksandra BabichevaJason X-J Yuan
Jul 13, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hicham Labazi, Aaron J Trask
Oct 28, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Pritesh P JainJason X-J Yuan

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