TY - JOUR
T1 - Autocrine/paracrine secretion of IL-6 family cytokines causes angiotensin II-induced delayed STAT3 activation
AU - Sano, Motoaki
AU - Fukuda, Keiichi
AU - Kodama, Hiroaki
AU - Takahashi, Toshiyuki
AU - Kato, Takahiro
AU - Hakuno, Daihiko
AU - Sato, Toshihiko
AU - Manabe, Tomohiro
AU - Tahara, Satoko
AU - Ogawa, Satoshi
N1 - Funding Information:
This study was supported in part by research grants of the “Research for the Future” Program from the Japan Society for the Promotion of Science (JSPS-RFTF97I00201), and research grants from the Ministry of Education, Science and Culture, Japan, Health Science Research Grants for Advanced Medical Technology from the Ministry of Welfare, Japan. The authors acknowledge Kio Naka-maru for technical assistance.
PY - 2000/3/24
Y1 - 2000/3/24
N2 - We recently reported that angiotensin II (AngII) biphasically activates the JAK/STAT pathway and induces delayed phosphorylation of STAT3 in the late stage (120 min) in cardiomyocytes. This study was designed to determine the mechanism of delayed phosphorylation of STAT3. Conditioned medium prepared from AngII-stimulated cardiomyocytes could reproduce the tyrosine phosphorylation of STAT3 at 5 min. This delayed phosphorylation was almost completely inhibited by anti-gp130 blocking antibody RX435, but not by TAK044 (ET-A/B-R antagonist), prazosin, or propranolol. AngII induced phosphorylation of gp130 in the late stage, which was temporally in parallel with the delayed phosphorylation of STAT3. AngII augmented IL-6, CT-1, and LIF mRNA expression at 30-60 min, but not CNTF expression. AngII increased IL-6 protein levels by 3-fold in the conditioned media at 2 h compared with the control. These findings indicated that AngII-induced delayed activation of STAT3 is caused by autocrine/paracrine secreted IL-6 family cytokines. (C) 2000 Academic Press.
AB - We recently reported that angiotensin II (AngII) biphasically activates the JAK/STAT pathway and induces delayed phosphorylation of STAT3 in the late stage (120 min) in cardiomyocytes. This study was designed to determine the mechanism of delayed phosphorylation of STAT3. Conditioned medium prepared from AngII-stimulated cardiomyocytes could reproduce the tyrosine phosphorylation of STAT3 at 5 min. This delayed phosphorylation was almost completely inhibited by anti-gp130 blocking antibody RX435, but not by TAK044 (ET-A/B-R antagonist), prazosin, or propranolol. AngII induced phosphorylation of gp130 in the late stage, which was temporally in parallel with the delayed phosphorylation of STAT3. AngII augmented IL-6, CT-1, and LIF mRNA expression at 30-60 min, but not CNTF expression. AngII increased IL-6 protein levels by 3-fold in the conditioned media at 2 h compared with the control. These findings indicated that AngII-induced delayed activation of STAT3 is caused by autocrine/paracrine secreted IL-6 family cytokines. (C) 2000 Academic Press.
KW - Angiotensin II
KW - Autocrine/paracrine
KW - STAT3
KW - Signal transduction
KW - gp130
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U2 - 10.1006/bbrc.2000.2364
DO - 10.1006/bbrc.2000.2364
M3 - Article
C2 - 10720495
AN - SCOPUS:0034708368
SN - 0006-291X
VL - 269
SP - 798
EP - 802
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -