Abstract
The pleiotrophic effects of angiotensin II (Ang II) play important roles in astrocyte growth and inflammatory responses. We investigated whether Ang II induces astrocyte growth and interleukin-6 (IL-6) mRNA expression in rat cerebellar astrocytes through Janus kinase 2-signal transduction activator of transcription (JAK2-STAT3). Ang II increased JAK2 and STAT3 phosphorylation in a time- and a dose-dependent manner. One hundred nanomolar Ang II induced maximal phosphorylation of both JAK2 and STAT3 between 15 min and 30 min. The Ang II-mediated phosphorylation of both JAK2 and STAT3 was blocked by AG490, a selective JAK2 inhibitor. Losartan, a selective AT1 receptor antagonist, inhibited Ang II-mediated JAK2 and STAT3 phosphorylation, while pretreatment with an AT2 receptor blocker, PD123319, was ineffective. Ang II increased the mRNA expression of IL-6 in a concentration-and time-dependent manner. Maximal IL-6 mRNA expression occurred with 100 nM Ang II, and the peak effect occurred in a biphasic manner a...