Korean J Intern Med.  2016 Jan;31(1):116-124. 10.3904/kjim.2016.31.1.116.

Angiotensin III increases monocyte chemoattractant protein-1 expression in cultured human proximal tubular epithelial cells

  • 1Division of Nephrology, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
  • 2Division of Nephrology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea. dr52916@catholic.ac.kr
  • 3Renal Research Laboratory, Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 4Department of Medicine, Stony Brook University of New York, Stony Brook, NY, USA.


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).
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.
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.
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.


Angiotensin III; Kidney tubules; Chemokine CCL2; Mitogen-activated protein kinases; Transcription factors

MeSH Terms

Angiotensin II Type 1 Receptor Blockers/pharmacology
Angiotensin III/*pharmacology
Cell Line
Chemokine CCL2/*metabolism
Dose-Response Relationship, Drug
Epithelial Cells/*drug effects/metabolism
JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
Kidney Tubules, Proximal/*drug effects/metabolism
Protein Kinase Inhibitors/pharmacology
Signal Transduction/drug effects
Time Factors
Transcription Factor AP-1/metabolism
p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
Angiotensin II Type 1 Receptor Blockers
Angiotensin III
Chemokine CCL2
Protein Kinase Inhibitors
JNK Mitogen-Activated Protein Kinases
Transcription Factor AP-1
p38 Mitogen-Activated Protein Kinases
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