Angiotensin III induces signal transducer and activator of transcription 3 and interleukin-6 mRNA levels in cultured rat astrocytes

INTRODUCTION: Recently we established that pro-inflammatory actions of angiotensin (Ang) II in astrocytes involved Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and interleukin-6 (IL-6). MATERIALS AND METHODS: In our current study, we determined in brainstem and cerebellum whether Ang III also activates STAT3 leading to IL-6 mRNA expression and astrocyte proliferation. RESULTS: Ang III induced STAT3 phosphorylation in a concentration- and time-dependent manner. Significant STAT3 phosphorylation was rapid and was maximal within 10 min, and with 100 nM Ang III. The Ang AT1 receptor was shown to mediate this action of Ang III. Ang III also significantly induced IL-6 mRNA expression within an hour, and maximal Ang III-mediated IL-6 mRNA expression occurred in the presence of 100 nM Ang III. Ang III-mediated IL-6 mRNA expression occurred by the interaction of the peptide with the Ang AT1 receptor and was mediated by STAT3. In addition, STAT3 was shown to mediate Ang III astrocyte proliferation. CONCLUSIONS: These findings suggest that Ang III, similar to Ang II, has pro-inflammatory effects since it induces STAT3 leading to an induction of IL-6 mRNA expression, outcomes that lend relevance to the physiological importance of central Ang III.