ERK and p38 MAPK, but not NF-κB, Are Critically Involved in Reactive Oxygen Species–Mediated Induction of IL-6 by Angiotensin II in Cardiac Fibroblasts

• DOI: 10.1161/hh2001.098873
• Publication Date: 2007-09-28T18:32:49Z
• Authors: Motoaki Sano; Keiichi Fukuda; Toshihiko Sato; Haruko Kawaguchi; Makoto Suematsu; Satoshi Matsuda; Shigeo Koyasu; Hideo Matsui; Keiko Yamauchi-Ta...; Masaki Harada; Yoshihiko Saito; Satoshi Ogawa
• Keywords: Pyrrolidine dithiocarbamate

We recently reported that angiotensin II (Ang II) induced IL-6 mRNA expression in cardiac fibroblasts, which played an important role Ang II–induced hypertrophy paracrine fashion. The present study investigated the regulatory mechanism of gene expression, focusing especially on reactive oxygen species (ROS)-mediated signaling fibroblasts. increased intracellular ROS and increase was completely inhibited by AT-1 blocker candesartan NADH/NADPH oxidase inhibitor diphenyleneiodonium (DPI). first confirmed antioxidant N -acetylcysteine, superoxide scavenger Tiron, DPI suppressed expression. Because we observed exogenous H 2 O also mRNA, pathways downstream were compared. II, as well , activated ERK, p38 MAPK, JNK, significantly -acetylcysteine DPI. In contrast with however, did not influence phosphorylation degradation IκB-α/β or nuclear translocation p65, nor it NF-κB promoter activity. PD98059 SB203580 Truncation mutational analysis showed CRE cis -element NF-κB–binding site for basal IL-6, but II. phosphorylated CREB through ERK MAPK pathway a ROS-sensitive manner. Collectively, these data indicated stimulated production via AT1 receptor oxidase, mediated activation MAPKs, culminated CRE-dependent, NF-κB–dependent,