Cross-talk between angiotensin II and interleukin-6-induced signaling through Stat3 transcription factor.
In cultured neonatal rat cardiac fibroblasts and CHO-K1 cells expressing angiotensin II (Ang II) type 1 receptors (AT1) (T3CHO/AT1A cell line), Ang II induced a delayed tyrosine phosphorylation of Stat3 (Signal Transducers and Activators of Transcription) with maximal activation at 2 h. This was in contrast to the rapid tyrosine phosphorylation (15-30 min) of Stat3 by the cytokine interleukin-6 (IL-6). Using T3CHO/AT1A cells, we tested the hypothesis that the delayed tyrosine phosphorylation of Stat3 by Ang II resulted from the induction of an inhibitory pathway (0-30 min) prior to activation (1-2 h). In support of this hypothesis, we observed that a short treatment of cells with Ang II transiently inhibited the IL-6-induced Stat3 tyrosine phosphorylation. The inhibitory effect of Ang II could be attenuated by exposing the cells to a specific inhibitor of MAP kinase kinase 1, PD98059. Such modulatory cross-talk between Ang II and IL-6 may have relevance in pathophysiological conditions such as cardiac hypertrophy, and in acute phase and inflammatory responses.
Bhat
G J
GJ
Pen State University College of Medicine, Weis Center for Research, Danville, PA 17822, USA.
Baker
K M
KM
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494088:Stat3 protein, rat; D015534:Trans-Activators; D000804:Angiotensin II; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases