title: Angiotensin III increases monocyte chemoattractant protein-1 expression in cultured human proximal tubular epithelial cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Sun Ae
authors.initials: SA
authors.lastname: Yoon
authors.affiliation: Renal Research Laboratory, Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Han
authors.affiliation: Department of Medicine, Stony Brook University of New York, Stony Brook, NY, USA.
authors.forename: Hyun-Bae
authors.initials: HB
authors.lastname: Chun
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D047428:Protein Kinase Inhibitors; D018808:Transcription Factor AP-1; D000805:Angiotensin III; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Angiotensin III; Chemokine CCL2; Kidney tubules; Mitogen-activated protein kinases; Transcription factors