C-reactive protein induces pulmonary artery smooth cell proliferation via modulation of ERK1/2, Akt and NF-kappaB pathways.

Abstract

C-reactive protein (CRP) is a biomarker of systemic inflammation, which is also associated with pulmonary artery disease. However, the impact of CRP on cell proliferation of the pulmonary arterial wall has been investigated less. We, therefore, examined the effects and potential mechanisms of CRP on proliferation in human pulmonary artery smooth muscle cells (hPASMC). HPASMCs were cultured and stimulated by different concentrations of CRP (5 - 200 microg/mL) for 24 hours. The effects of CRP on proliferation of hPASMCs were examined using the BrDU incorporation assay, and the potential signal pathways including ERK1/2, Akt and NF-kappaB involved in hPASMCs' proliferation were evaluated by the Western blot and electrophoretic mobility shift assays. CRP significantly increased proliferation of hPASMCs with a dose-dependent fashion (1.13-fold increase in CRP 5 microg/mL, and 1.84-fold increase in CRP 200 microg/mL versus controls, p < 0.05 and 0.01, respectively). Additionally, CRP could enhance the expression of Akt and ERK1/2 phosphorylation, but had no effects on total protein. Moreover, CRP resulted in the activation of NF-kappaB significantly, which was diminished by PI3K inhibitor wortmannin. The increased expression of phosphorylated ERK1/2 was inhibited by MEK inhibitor PD98095, whereas no such effects of NF-kappaB inhibitor Bay117082 on the expression of Akt and ERK1/2 was found. The data suggest that CRP directly impacts proliferation of hPASMCs via modulation of Akt, ERK1/2, and NF-kappaB pathways, which may have important implications for treating pulmonary arterial disease.