PMID- 16155367
OWN - NLM
STAT- MEDLINE
DCOM- 20051205
LR  - 20131121
IS  - 1018-1172 (Print)
IS  - 1018-1172 (Linking)
VI  - 42
IP  - 6
DP  - 2005 Nov-Dec
TI  - Inhibition of tumor-necrosis-factor-alpha induced endothelial cell activation by 
      a new class of PPAR-gamma agonists. An in vitro study showing 
      receptor-independent effects.
PG  - 509-16
AB  - Proinflammatory cytokines and adhesion molecules expressed by endothelial cells 
      (ECs) play a critical role in initiating and promoting atherosclerosis. Agents 
      that oppose these inflammatory effects in vascular cells include peroxisome 
      proliferator-activated receptor-gamma (PPAR-gamma) ligands, including 
      15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and synthetic 
      thiazolidinediones. Recently, a new structural class of potent PPAR-gamma 
      agonists, 1,1-bis(3'-indolyl)-1-(p-substituted phenyl) methanes, has been 
      characterized. The purpose of this study was to evaluate the anti-inflammatory 
      effects of two PPAR-gamma-active members of this class, 
      1,1-bis(3'-indolyl)-1-(p-t-butylphenyl)methane (DIM-C-pPhtBu) and 
      1,1-bis(3'-indolyl)-1-(p-biphenyl)methane (DIM-C-pPhC(6)H(5)), in ECs in vitro. 
      Pretreatment of ECs with DIM-C-pPhC(6)H(5), DIM-C- pPhtBu, or 15d-PGJ2 decreased 
      tumor necrosis factor-alpha (TNF-alpha)-induced intercellular adhesion molecule 
      (ICAM)-1 expression in a concentration-dependent manner. At a concentration of 10 
      microM, DIM-C-pPhtBu and DIM-C-pPhC(6)H(5) decreased ICAM-1 expression by 77.5 
      and 71.3%, respectively, and comparable inhibition (84.4%) was observed for 10 
      microM 15d-PGJ2 (p < 0.05). In contrast, 10 microM ciglitazone and 
      DIM-C-pPhCH(3), which exhibits low PPAR-gamma agonist activity, were inactive. 
      The two new PPAR-gamma agonists and 15d-PGJ2 also inhibited TNF-alpha-induced 
      interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production in 
      supernatants of TNF-alpha-stimulated ECs, whereas ciglitazone and DIM-C-pPhCH(3) 
      did not decrease TNF-alpha-induced expression of these two proteins. This new 
      structural class of PPAR-gamma agonists inhibited the expression of ICAM-1 and 
      the production of IL-6 and MCP-1 in TNF-alpha-activated ECs at lower 
      concentrations than other synthetic PPAR-gamma agonists, suggesting the potential 
      clinical utility of 1,1-bis(3'-indolyl)-1-(p-substituted phenyl) methanes for 
      decreasing endothelial inflammation.
FAU - Calabro, Paolo
AU  - Calabro P
AD  - Brown Foundation Institute of Molecular Medicine for the Prevention of Human 
      Diseases, University of Texas-Houston Health Science Center, Houston, Tex., USA.
FAU - Samudio, Ismael
AU  - Samudio I
FAU - Safe, Stephen H
AU  - Safe SH
FAU - Willerson, James T
AU  - Willerson JT
FAU - Yeh, Edward T H
AU  - Yeh ET
LA  - eng
GR  - ES0-9106/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050909
PL  - Switzerland
TA  - J Vasc Res
JT  - Journal of vascular research
JID - 9206092
RN  - 0 (1,1-bis(3'-indolyl)-1-(4-biphenyl)methane)
RN  - 0 (1,1-bis(3'-indolyl)-1-(4-t-butylphenyl)methane)
RN  - 0 (15-deoxyprostaglandin J2)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Indoles)
RN  - 0 (Interleukin-6)
RN  - 0 (PPAR gamma)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects/*physiology
MH  - Humans
MH  - Indoles/administration & dosage/*pharmacology
MH  - Intercellular Adhesion Molecule-1/drug effects
MH  - Interleukin-6/antagonists & inhibitors
MH  - PPAR gamma/*agonists
MH  - Prostaglandin D2/analogs & derivatives/pharmacology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/*pharmacology
MH  - Umbilical Veins/cytology
EDAT- 2005/09/13 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/09/13 09:00
PHST- 2005/01/18 00:00 [received]
PHST- 2005/06/21 00:00 [accepted]
PHST- 2005/09/13 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/09/13 09:00 [entrez]
AID - 88260 [pii]
AID - 10.1159/000088260 [doi]
PST - ppublish
SO  - J Vasc Res. 2005 Nov-Dec;42(6):509-16. doi: 10.1159/000088260. Epub 2005 Sep 9.