PMID- 10690939
OWN - NLM
STAT- MEDLINE
DCOM- 20000306
LR  - 20190725
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 49
IP  - 2
DP  - 2000 Feb
TI  - Inhibitory effect of troglitazone on tumor necrosis factor alpha-induced 
      expression of monocyte chemoattractant protein-1 in human mesangial cells.
PG  - 163-6
AB  - Insulin resistance is one of the risk factors for the progression of 
      atherosclerosis and glomerulosclerosis. Recently, the new oral 
      insulin-sensitizing agent troglitazone has been thought to offer potential in the 
      treatment of diabetes. If adopted for this use, it might be helpful in protecting 
      against the development of atherosclerosis and microvascular complications via 
      its improvement of insulin resistance. However, it has not yet been clarified 
      whether troglitazone acts directly on the vascular cells and inhibits the 
      progression of atherosclerosis, including glomerulosclerosis. Meanwhile, monocyte 
      chemoattractant protein-1 (MCP-1) is known to play an important role in the 
      pathogenesis of atherosclerosis and glomerulosclerosis through the induction of 
      monocyte migration. Therefore, we investigated the effect of troglitazone on the 
      expression of MCP-1 in human mesangial cells (HMCs). HMCs were treated with or 
      without troglitazone (1 or 10 micromol/L) in the presence or absence of tumor 
      necrosis factor alpha (TNF-alpha) at various concentrations (50 or 500 ng/mL), 
      and then MCP-1 secretion from the HMCs was measured. We found that TNF-alpha 
      increased the secretion of MCP-1 by 55-fold versus the control and troglitazone 
      significantly inhibited this TNF-alpha-induced increase in MCP-1 secretion 
      (49.3%). Moreover, Northern blot analysis showed that troglitazone decreased the 
      MCP-1 mRNA level in HMCs. We demonstrated that alpha-tocopherol also inhibited 
      TNF-alpha-induced MCP-1 production in HMCs, although its effects were not as 
      strong as troglitazone. The present study indicates that troglitazone may prevent 
      the progression of atherosclerosis by inhibiting MCP-1 expression in mesangial 
      cells.
FAU - Ohta, M Y
AU  - Ohta MY
AD  - First Department of Internal Medicine, School of Medicine, Kanazawa University, 
      Ishikawa, Japan.
FAU - Nagai, Y
AU  - Nagai Y
FAU - Takamura, T
AU  - Takamura T
FAU - Nohara, E
AU  - Nohara E
FAU - Kobayashi, K
AU  - Kobayashi K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromans)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1406-18-4 (Vitamin E)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - Blotting, Northern
MH  - Cell Count/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Chromans/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glomerular Mesangium/cytology/drug effects/*metabolism
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Thiazoles/*pharmacology
MH  - *Thiazolidinediones
MH  - Troglitazone
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology
MH  - Vitamin E/pharmacology
EDAT- 2000/02/26 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
AID - S0026-0495(00)91143-0 [pii]
AID - 10.1016/s0026-0495(00)91143-0 [doi]
PST - ppublish
SO  - Metabolism. 2000 Feb;49(2):163-6. doi: 10.1016/s0026-0495(00)91143-0.