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

作者：Kim Hyung Wook; Kim Young Ok; Yoon Sun Ae; Han Jeong Sun; Chun Hyun Bae; Kim Young Soo^*

来源：Korean Journal of Internal Medicine, 2016, 31(1): 116-124.

DOI：10.3904/kjim.2016.31.1.116

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

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.

• 出版日期2016-1