Angiotensin III increases monocyte chemoattractant protein-1 expression in cultured human proximal tubular epithelial cells.
10.3904/kjim.2016.31.1.116
- Author:
Hyung Wook KIM
1
;
Young Ok KIM
;
Sun Ae YOON
;
Jeong Sun HAN
;
Hyun Bae CHUN
;
Young Soo KIM
Author Information
1. Division of Nephrology, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
- Publication Type:Original Article
- Keywords:
Angiotensin III;
Kidney tubules;
Chemokine CCL2;
Mitogen-activated protein kinases;
Transcription factors
- MeSH:
Angiotensin II Type 1 Receptor Blockers/pharmacology;
Angiotensin III/*pharmacology;
Cell Line;
Chemokine CCL2/*metabolism;
Dose-Response Relationship, Drug;
Epithelial Cells/*drug effects/metabolism;
Humans;
JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism;
Kidney Tubules, Proximal/*drug effects/metabolism;
Phosphorylation;
Protein Kinase Inhibitors/pharmacology;
Signal Transduction/drug effects;
Time Factors;
Transcription Factor AP-1/metabolism;
Up-Regulation;
p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
- From:The Korean Journal of Internal Medicine
2016;31(1):116-124
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND/AIMS: We investigated whether angiotensin III (Ang III) is involved in monocyte recruitment through regulation of the chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal tubular epithelial cells (HK-2 cells). METHODS: We measured MCP-1 levels in HK-2 cells that had been treated with various concentrations of Ang III and Ang II type-1 (AT1) receptor antagonists at various time points. The phosphorylation states of p38, c-Jun N-terminal kinases (JNK), and extracellular-signal-regulated kinases were measured in Ang III-treated cells to explore the mitogen-activated protein kinase (MAPK) pathway. MCP-1 levels in HK-2 cell-conditioned media were measured after pre-treatment with the transcription factor inhibitors curcumin or pyrrolidine dithiocarbamate. RESULTS: Ang III increased MCP-1 protein production in dose- and time-dependent manners in HK-2 cells, which was inhibited by the AT1 receptor blocker losartan. p38 MAPK activity increased significantly in HK-2 cells exposed to Ang III for 30 minutes, and was sustained at higher levels after 60 minutes (p < 0.05). Total phosphorylated JNK protein levels tended to increase 20 minutes after stimulation with Ang III. Pre-treatment with a p38 inhibitor, a JNK inhibitor, or curcumin significantly inhibited Ang III-induced MCP-1 production. CONCLUSIONS: Ang III increases MCP-1 synthesis via stimulation of intracellular p38 and JNK MAPK signaling activity and subsequent activated protein-1 transcriptional activity in HK-2 cells.
