Objective: Interferon gamma (IFN-γ) was shown to induce CD40 and CD40L expression on endothelial cells (ECs) and consequently to promote neutrophil adhesion. The pro- and anti-inflammatory effects of estrogens are well recognized but their role on the regulation of CD40 and CD40L expression on ECs remains undefined. Methods and results: Treatment of porcine aortic endothelial cells (PAEC) with IFN-γ for 24 h enhanced CD40 and CD40L expression by 97% and 78%, respectively. Pretreatment of PAEC with 17-beta-estradiol (17βE) for 24 h prevented the latter expression of CD40/CD40L. Treatment of PAEC with antisense oligomers targeting ERα mRNA attenuated the ability of 17βE to inhibit the IFN-γ-induced CD40 and CD40L protein expression. The IFN-γ activation pathway of CD40 is known to involve the phosphorylation of the Janus activated kinase (JAK) and the signal transducer and activator of transcription 1 (Stat1). 17βE, acting via the estrogen receptor α (ERα), abrogated IFN-γ-mediated effects on Stat1 but failed to inhibit Jak1 and Jak2 phosphorylation. Furthermore, 17βE prevented neutrophil adhesion induced by IFN-γ. Conlusion: In summary, 17βE binding to ERα blocked IFN-γ-induced Stat1 phosphorylation, CD40 and CD40L protein expression, and neutrophil adhesion onto ECs. © 2006 European Society of Cardiology.
Geraldes, P., Gagnon, S., Hadjadj, S., Merhi, Y., Sirois, M. G., Cloutier, I., & Tanguay, J. F. (2006). Estradiol blocks the induction of CD40 and CD40L expression on endothelial cells and prevents neutrophil adhesion: An ERα-mediated pathway. Cardiovascular Research, 71(3), 566–573. https://doi.org/10.1016/j.cardiores.2006.05.015