KMID : 0338420160310010116
|
|
The Korean Journal of Internal Medicine 2016 Volume.31 No. 1 p.116 ~ p.124
|
|
Angiotensin III increases monocyte chemoattractant protein-1 expression in cultured human proximal tubular epithelial cells
|
|
Kim Hyung-Wook
Kim Young-Ok Yoon Sun-Ae Han Jeong-Sun Chun Hyun-Bae Kim Young-Soo
|
|
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.
|
|
KEYWORD
|
|
Angiotensin III, Kidney tubules, Chemokine CCL2, Mitogen-activated protein kinases, Transcription factors
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|