PMID- 11473635
OWN - NLM
STAT- MEDLINE
DCOM- 20011011
LR  - 20161124
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 60
IP  - 2
DP  - 2001 Aug
TI  - Lipoprotein-X stimulates monocyte chemoattractant protein-1 expression in 
      mesangial cells via nuclear factor-kappa B.
PG  - 520-32
AB  - BACKGROUND: Lipoprotein-X (Lp-X) is an abnormal lipoprotein found in the plasma 
      of patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency. 
      The majority of patients with this disorder develop progressive 
      glomerulosclerosis. One key event in the pathogenesis of glomerulosclerosis is 
      the infiltration of monocytes into affected glomeruli. Mesangial cells can 
      synthesize and secrete monocyte chemoattractant protein-1 (MCP-1), an important 
      chemoattractant for monocytes. The objective of the present study was to examine 
      the effect of Lp-X on MCP-1 expression in mesangial cells leading to an enhanced 
      monocyte chemotaxis and to elucidate the mechanisms involved in this process. 
      METHODS: Lp-X was isolated from the plasma of a patient with familial LCAT 
      deficiency. After rat mesangial cells were incubated with Lp-X for four or six 
      hours, the expression of MCP-1 mRNA was determined by nuclease protection assay, 
      and MCP-1 protein was measured by Western immunoblotting analysis. Monocyte 
      chemotaxis was determined by using a Micro Chemotaxis Chamber. RESULTS: Lp-X (50 
      to 100 nmol/mL) stimulated mesangial cell MCP-1 mRNA expression (137 to 220%) and 
      MCP-1 protein levels (233 to 375%). Conditioned media collected from Lp-X-treated 
      mesangial cells stimulated human acute monocytic leukemia (THP-1) monocyte 
      chemotaxis (165 to 200%). The increase in MCP-1 expression in mesangial cells was 
      associated with an elevation of intracellular diacylglycerol levels, and 
      activation of protein kinase C (PKC) as well as nuclear factor-kappa B (NF-kappa 
      B). CONCLUSION: These results suggest that Lp-X participates in the pathogenesis 
      of glomerulosclerosis and subsequent renal failure in familial LCAT deficient 
      patients by stimulating monocyte infiltration via a mechanism involving mesangial 
      MCP-1 expression.
FAU - Lynn, E G
AU  - Lynn EG
AD  - Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong 
      Kong SAR, China.
FAU - Siow, Y L
AU  - Siow YL
FAU - Frohlich, J
AU  - Frohlich J
FAU - Cheung, G T
AU  - Cheung GT
FAU - O, K
AU  - O K
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 (Calcium Channel Blockers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Diglycerides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Lipoprotein-X)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Pyrroles)
RN  - 0 (RNA, Messenger)
RN  - 151342-35-7 (Ro 32-0432)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EE92BBP03H (Diltiazem)
RN  - H88EPA0A3N (Staurosporine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium Channel Blockers/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Chemotaxis, Leukocyte/drug effects/immunology
MH  - Cholesterol/metabolism
MH  - Diglycerides/metabolism
MH  - Diltiazem/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Foam Cells/metabolism
MH  - Gene Expression/drug effects/immunology
MH  - Genes, Recessive
MH  - Glomerular Mesangium/cytology/*metabolism
MH  - Glomerulosclerosis, Focal Segmental/immunology/metabolism
MH  - Humans
MH  - Indoles/pharmacology
MH  - Lecithin Cholesterol Acyltransferase Deficiency/genetics/immunology/*metabolism
MH  - Lipoprotein-X/isolation & purification/*pharmacology
MH  - Male
MH  - Molecular Sequence Data
MH  - Monocytes/cytology
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Phosphatidylcholines/metabolism
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Pyrroles/pharmacology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Staurosporine/pharmacology
MH  - Type C Phospholipases/metabolism
EDAT- 2001/07/28 10:00
MHDA- 2001/10/12 10:01
CRDT- 2001/07/28 10:00
PHST- 2001/07/28 10:00 [pubmed]
PHST- 2001/10/12 10:01 [medline]
PHST- 2001/07/28 10:00 [entrez]
AID - S0085-2538(15)47897-4 [pii]
AID - 10.1046/j.1523-1755.2001.060002520.x [doi]
PST - ppublish
SO  - Kidney Int. 2001 Aug;60(2):520-32. doi: 10.1046/j.1523-1755.2001.060002520.x.