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Tumor necrosis factor mediated release of platelet-derived growth factor from bovine cerebral microvascular
1Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, China.
Aim:
To study the effect of tumor necrosis factor (TNF) on platelet-derived growth factor (PDGF) release from bovine cerebral microvascular endothelial cells (BCMEC), and the protection of drugs on proliferation of bovine cerebral microvascular smooth muscle cells (BCMSMC).
Methods:
BCMEC and BCMSMC were cultured in vitro. Effects of TNF on PDGF release from BCMEC were investigated by crystal violet assay.
Results:
TNF did not promote the proliferation of BCMSMC directly. But the postculture medium of BCMEC stimulated by TNF promoted the proliferation of BCMSMC in a concentration (5-20 micrograms.L-1)-dependent manner, and the mitogenic activity was neutralized by antibody to PDGF. The BCMSMC proliferation was increased 34 +/- 4% over control by TNF (20 micrograms.L-1). Imperatorin (Imp), iso-imperatorin (iso-Imp), and 6-(alpha, alpha-phenylacetylpiperazinyl) phenyl-5-methyl-4, 5-dihydro-3 (2H)-pyridazinone (PMDP) 1-100 mumol.L-1 did not affect the PDGF release from BCMEC stimulated by TNF, but inhibited the BCMSMC proliferation promoted by PDGF concentration-dependently.
Conclusion:
TNF promoted PDGF release from BCMEC. The proliferation of BCMSMC stimulated by TNF must be mediated by growth factor, such as PDGF. Imp, iso-Imp, PMDP inhibited proliferation of BCMSMC stimulated by PDGF.