Role of ERα in the immunomodulatory effects of 4HT
To study the molecular mechanism of high-dose 4HT responses, we analyzed the involvement of ERα in 4HT transcriptional activity using macrophages isolated from ERαKO animals. 10 µM 4HT induced a 6-fold increase inVegfα mRNA in ERα-KO macrophages (Figure 2), similarly with wild-type cells, while smaller concentrations of 4HT did not induce any effect (data not shown). As expected, E2 did not trigger transcriptional responses in the absence of ERα and, as consequence, also 4HT interference and synergistic effects with E2 were not detected. These data strongly indicated that the transcriptional activity of high 4HT levels is ERα-independent.