Premium
Angiotensin II Induces JAK2 and IL‐6 in Brainstem Rat Astrocytes
Author(s) -
KANDALAM UMADEVI,
CLARK MICHELLE A
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.581.5
Subject(s) - losartan , angiotensin ii , medicine , endocrinology , secretion , phosphorylation , chemistry , tyrosine phosphorylation , receptor , biology , microbiology and biotechnology
Tyrosine kinases and mitogen‐activated protein kinases are known mediators of angiotensin II (Ang II) effects in cultured rat astrocytes. In this study, we investigated whether Ang II induced Janus kinase (JAK) 2 phosphorylation and interleukin‐6 (IL‐6) secretion in brainstem rat astrocytes. Ang II increased JAK2 phosphorylation in a time‐ and concentration‐dependent manner. Maximal effect was observed at 15 min with 100 nM Ang II. Losartan (10 µM), an AT 1 receptor antagonist, inhibited Ang II‐mediated JAK2 phosphorylation, while 10 μM PD123319, an AT 2 receptor blocker, was ineffective. The JAK2 inhibitor, AG490 (50 µM) prevented Ang II JAK2 phosophorylation. Ang II (100 nM) also stimulated IL‐6 secretion from brainstem astrocytes with maximal secretion at 48 hrs. Losartan decreased Ang II‐induced IL‐6 secretion while PD123319 was ineffective. Interestingly, AG490 reduced Ang II‐stimulated IL‐6 secretion. These findings showed for the first time that Ang II induced JAK2 phosphorylation and IL‐6 secretion through activation of the Ang II AT 1 receptor in brainstem astrocytes. In addition, Ang II stimulated IL‐6 secretion through the JAK‐2 pathway in brainstem astrocytes. These results provide new insights into Ang II signaling in astrocytes. (Support: NHLBL HLO77199 and by Nova Southeastern University President's Faculty Research & Development Grant.).