PMID- 11287779
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20171101
IS  - 1660-8151 (Print)
IS  - 1660-8151 (Linking)
VI  - 87
IP  - 4
DP  - 2001 Apr
TI  - Effect of high glucose concentration on the synthesis of monocyte chemoattractant 
      protein-1 in human peritoneal mesothelial cells: involvement of protein kinase C.
PG  - 346-51
AB  - Human peritoneal mesothelial cells (HMC) contribute to the activation and control 
      of inflammatory processes in the peritoneum by their potential to produce various 
      inflammatory mediators. The present study was designed to assess the effect of 
      glucose, the osmotic active compound in most commercially available peritoneal 
      dialysis fluids, on the synthesis of the C-C chemokine monocyte chemoattractant 
      protein-1 (MCP-1) in cultured HMC. The MCP-1 concentration in the cell 
      supernatants was determined by enzyme-linked immunosorbent assay and the MCP-1 
      mRNA expression was examined using Northern blot analysis. Incubation of HMC with 
      glucose (30-120 mM) resulted in a time- and concentration-dependent increase in 
      MCP-1 protein secretion and mRNA expression. After 24 h the MCP-1 synthesis was 
      increased from 2.8 +/- 0.46 to 4.2 +/- 0.32 ng/10(5) cells (n = 5, p < 0.05) in 
      HMC treated with 60 mM glucose. In contrast, osmotic control media containing 
      either the metabolically inert monosaccharide mannitol or NaCl did not influence 
      MCP-1 production. The stimulating effect of high glucose on MCP-1 expression in 
      HMC was mimicked by activation of protein kinase C (PKC) with the phorbol ester 
      PMA (20 nM). Coincubation of the cells with glucose and the specific PKC 
      inhibitor Ro 31-8220 completely blunted glucose-mediated MCP-1 expression. In 
      summary, our results indicate that glucose induces MCP-1 synthesis by a 
      PKC-dependent pathway. Since osmotic control media did not increase MCP-1 
      release, it is suggested that the effect of glucose is mainly related to 
      metabolism and not to hyperosmolarity. These data may in part explain elevated 
      steady-state levels of MCP-1 found in the dialysis effluent of continuous 
      ambulatory peritoneal dialysis patients.
CI  - Copyright 2001 S. Karger AG, Basel
FAU - Haslinger, B
AU  - Haslinger B
AD  - Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universitat, 
      Munchen, Deutschland.
FAU - Mandl-Weber, S
AU  - Mandl-Weber S
FAU - Sellmayer, A
AU  - Sellmayer A
FAU - Lederer, S R
AU  - Lederer SR
FAU - Sitter, T
AU  - Sitter T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Nephron
JT  - Nephron
JID - 0331777
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 3OWL53L36A (Mannitol)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/analysis/*genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/cytology/drug effects/*physiology
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Kinetics
MH  - Mannitol/pharmacology
MH  - Peritoneal Cavity
MH  - Protein Kinase C/*metabolism
MH  - RNA, Messenger/genetics
MH  - Sodium Chloride/pharmacology
MH  - Transcription, Genetic/*drug effects
EDAT- 2001/04/05 10:00
MHDA- 2001/04/05 10:01
CRDT- 2001/04/05 10:00
PHST- 2001/04/05 10:00 [pubmed]
PHST- 2001/04/05 10:01 [medline]
PHST- 2001/04/05 10:00 [entrez]
AID - 45941 [pii]
AID - 10.1159/000045941 [doi]
PST - ppublish
SO  - Nephron. 2001 Apr;87(4):346-51. doi: 10.1159/000045941.