Effect of High Glucose on the Expression of MCP-1 and VCAM-1 in Cultured Human Peritoneal Mesothelial Cells.
- Author:
Joon Seung LEE
1
;
Soon Bae KIM
;
Sang Koo LEE
;
Suk Hee YU
;
Jung Sik PARK
Author Information
1. Department of Internal Medicine, College of Medicine, University of Ulsan, Seoul, Korea. sklee2@www.amc.seoul.kr
- Publication Type:Original Article
- Keywords:
High glucose;
Human peritoneal mesothelial cell;
MCP-1;
VCAM-1;
Protein tyrosine kinase
- MeSH:
Blotting, Northern;
Cell Adhesion;
Cell Culture Techniques;
Cell Proliferation;
Cytokines;
Enzyme-Linked Immunosorbent Assay;
Genistein;
Glucose*;
Humans*;
Intercellular Signaling Peptides and Proteins;
Macrophages;
Mannitol;
Monocytes;
Peritoneal Cavity;
Peritoneal Dialysis;
Peritoneal Fibrosis;
Protein-Tyrosine Kinases;
RNA, Messenger;
Tyrosine;
Vascular Cell Adhesion Molecule-1*
- From:Korean Journal of Nephrology
2001;20(3):362-374
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: High glucose in peritoneal dialysis solution has been implicated in the pathogenesis of peritoneal fibrosis. Macrophages in peritoneal cavity seem to participate in the process of peritoneal fibrosis through the production of various cytokines and growth factors. Monocyte chemoattractant protein-1(MCP-1) plays a key role in the recruitment of monocytes toward the peritoneal cavity. Vascular cell adhesion molecule-1(VCAM-1) is assumed to be important in the transmigration of monocytes. MCP-1 and VCAM-1 can be induced by various cytokines and growth factors in human peritoneal mesothelial cells(HPMC). However, effect of high glucose on the expression of MCP-1 and VCAM-1 in HPMC has not been known well. METHODS: Cultured HPMC were conditioned with glucose(5-100mM) or mannitol for varying periods up to 7 days. Cell proliferation and mRNA expression of MCP-1 and VCAM-1 were assessed by MTT assay and Northern blot analysis respectively. MCP-1 protein was measured using ELISA. Chemotactic activity of high glucose-conditioned culture supernant were evaluated by chemotactic assay. Effect of protein tyrosine kinase(PTK) inhibitor on the high glucose-induced MCP-1 mRNA expression was examined. RESULTS: Glucose inhibited the cell proliferation in a time and dose dependent manner. Northern blot analysis showed that high glucose increased the MCP-1 mRNA expression in a time(2-7days) and dose(15-100mM) dependent manner, but not VCAM-1 mRNA expression. MCP-1 protein in cell culture supernant was also increased. Equivalent osmotic concentration of mannitol had no significant effect. High glucose-conditioned supernant had an increased chemotactic activity for monocyte, which was neutralized by specific anti-MCP-1 antibody. PTK inhibitors such as genistein and herbimycin A suppressed the high glucose-induced MCP-1 mRNA expression in a dose dependent manner. CONCLUSION: High glucose induced MCP-1 expression in HPMC partly via pathways involving PTK.
