PMID- 16518329
OWN - NLM
STAT- MEDLINE
DCOM- 20060518
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 69
IP  - 4
DP  - 2006 Feb
TI  - Prednisolone inhibits hyperosmolarity-induced expression of MCP-1 via NF-kappaB 
      in peritoneal mesothelial cells.
PG  - 736-46
AB  - The mechanism of peritoneal fibrosis in patients on continuous ambulatory 
      peritoneal dialysis (CAPD) is poorly elucidated. We investigated the cellular 
      mechanism of high-glucose-induced expression of monocyte chemoattractant 
      protein-1 (MCP-1), which is important in recruiting monocytes into the peritoneum 
      and progression of peritoneal fibrosis, and examined the inhibitory mechanism of 
      glucocorticoids. Rat peritoneal mesothelial cells were cultured in 
      high-glucose-containing medium and then analyzed for phosphorylation levels of 
      p42/44 and p38 mitogen-activated protein (MAP) kinases (MAPK), MAPK or 
      extracellular signal-regulated kinase kinase (MEK)1/2, c-Jun N-terminal kinase 
      (JNK)1/2, and protein kinase C (PKC) by Western blotting. Expression of MCP-1 was 
      examined by reverse transcription-polymerase chain reaction and enzyme-linked 
      immunosorbent assay, respectively. DNA-binding activity of nuclear factor 
      (NF)-kappaB was measured by electrophoretic mobility shift assay. High glucose 
      increased MCP-1 mRNA and MCP-1 protein expression. Although glucose increased 
      phosphorylation of MEK1/2, p42/44 MAPK, p38 MAPK, JNK1/2, and PKC, and 
      DNA-binding activity of NF-kappaB, its effect on MCP-1 expression was suppressed 
      only by PKC and NF-kappaB inhibitors. Mannitol caused a similar increase in PKC 
      and NF-kappaB activation and MCP-1 synthesis. Prednisolone increased 
      I-kappaB-alpha expression and inhibited glucose/mannitol-induced NF-kappaB DNA 
      binding and MCP-1 expression without affecting PKC phosphorylation. The 
      inhibitory effects of prednisolone on MCP-1 expression were reversed by 
      mifepristone, a glucocorticoid receptor antagonist. Our results indicate that 
      glucose induces MCP-1 mainly through hyperosmolarity by activating PKC and its 
      downstream NF-kappaB, and that such effect was inhibited by prednisolone, 
      suggesting the efficacy of prednisolone in preventing peritoneal fibrosis in 
      patients on CAPD.
FAU - Matsuo, H
AU  - Matsuo H
AD  - The Second Department of Internal Medicine, University of Occupational and 
      Environmental Health School of Medicine, and Kidney Center, University Hospital, 
      Kitakyushu, Japan.
FAU - Tamura, M
AU  - Tamura M
FAU - Kabashima, N
AU  - Kabashima N
FAU - Serino, R
AU  - Serino R
FAU - Tokunaga, M
AU  - Tokunaga M
FAU - Shibata, T
AU  - Shibata T
FAU - Matsumoto, M
AU  - Matsumoto M
FAU - Aijima, M
AU  - Aijima M
FAU - Oikawa, S
AU  - Oikawa S
FAU - Anai, H
AU  - Anai H
FAU - Nakashima, Y
AU  - Nakashima Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 320T6RNW1F (Mifepristone)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Enzyme Activation/drug effects
MH  - Epithelium/chemistry/physiopathology
MH  - Fibrosis/etiology/physiopathology/prevention & control
MH  - Gene Expression Regulation/*drug effects
MH  - Glucose/pharmacology
MH  - I-kappa B Proteins/genetics/metabolism
MH  - Mifepristone/pharmacology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/*physiology
MH  - Osmolar Concentration
MH  - Peritoneal Dialysis, Continuous Ambulatory
MH  - Peritoneum/*cytology/metabolism
MH  - Phosphorylation/drug effects
MH  - Prednisolone/*pharmacology
MH  - Protein Kinase C/metabolism
MH  - RNA, Messenger/analysis/genetics
MH  - Rats
EDAT- 2006/03/07 09:00
MHDA- 2006/05/19 09:00
CRDT- 2006/03/07 09:00
PHST- 2006/03/07 09:00 [pubmed]
PHST- 2006/05/19 09:00 [medline]
PHST- 2006/03/07 09:00 [entrez]
AID - S0085-2538(15)51540-8 [pii]
AID - 10.1038/sj.ki.5000131 [doi]
PST - ppublish
SO  - Kidney Int. 2006 Feb;69(4):736-46. doi: 10.1038/sj.ki.5000131.