Angiotensin III increases monocyte chemoattractant protein-1 expression in cultured human proximal tubular epithelial cells
The Korean Journal of Internal Medicine
;
: 116-124, 2016.
Article
in English
| WPRIM
| ID: wpr-220495
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Time Factors
/
Angiotensin III
/
Signal Transduction
/
Up-Regulation
/
Cell Line
/
Transcription Factor AP-1
/
Chemokine CCL2
/
JNK Mitogen-Activated Protein Kinases
/
P38 Mitogen-Activated Protein Kinases
Limits:
Humans
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2016
Type:
Article
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