Tanshinone IIA inhibits endothelin-1 production in TNF-α-induced brain microvascular endothelial cells through suppression of endothelin-converting enzyme-1 synthesis

摘要

Aim: To investigate the effects of tanshinone ⅡA (Tan ⅡA) on the regulation of the production of endothelin (ET)-1 (including large ET-1), mRNA levels of ET-1,endothelin-converting enzyme- 1 (ECE- 1), endothelin-A receptor (ETA) and endothelin-B receptor (ETB) induced by TNF-α in rat brain microvascular endo-thelial cells (BMVEC). Methods: The ET-1 release (including large ET-1) into the culture medium was determined by enzyme immunoassay. The levels of ET-1,ECE- 1, ETA, and ETB mRNA were measured by RT-PCR. Endothelin receptor bind-ing was also tested. Results: The induction of ET- 1 release by TNF-α from cul-tured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan ⅡA also caused a decrease in ETA receptor mRNA and ECE-1expression in a dose-dependent manner. Endothelin receptor binding was unal-tered in BMVEC stimulated with TNF-α alone or a combination of TNF-α and Tan ⅡA. Conclusion: These findings suggest that Tan ⅡA may inhibit ET-1 produc-tion in TNF-α-induced BMVEC through the suppression of ECE-1 synthesis.