Angiotensin II induced IL‐6 m RNA and cell growth through JAK2 in Rat Cerebellar Astrocytes

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 interlukin‐6 (IL‐6) mRNA levels in rat cerebellar astrocytes through Janus Kinase 2 (JAK2). Ang II increased JAK2 phosphorylation in a time‐ and a dose‐dependent manner. Maximal phosphorylation of JAK2 was observed with 100nM Ang II at 15 minutes. The phosphorylation of JAK2 was blocked by AG490, a JAK2 inhibitor. Losartan, a selective AT1 receptor antagonist, inhibited Ang II‐mediated JAK2 phosphorylation, while pretreatment with an AT2 receptor blocker 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 at 3 hours. Moreover, treatment with AG490 prevented Ang II‐induced IL‐6 mRNA levels, and Ang II‐induced astrocytes growth. The present study has demonstrated that Ang II induced the phosphorylation of JAK2 via the AT1 receptor in cerebellar astrocytes. In addition, our results suggest that JAK2 is an upstream signal that mediates Ang II‐induced IL‐6 expression and astrocyte growth. These findings represent a novel nonclassical mechanism of Ang II signaling in cerebellar astrocytes. (Support NHLBL HLO77199 and NSU PFDRG).