PMID- 11238525
OWN - NLM
STAT- MEDLINE
DCOM- 20010405
LR  - 20220408
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 86
IP  - 3
DP  - 2001 Mar
TI  - Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by 
      troglitazone: evidence for an anti-inflammatory effect and a potential 
      antiatherosclerotic effect in the obese.
PG  - 1306-12
AB  - To elucidate whether troglitazone exerts an antiinflammatory effect in humans, in 
      vivo, we investigated the suppression of nuclear factor kappaB (NFkappaB) in 
      mononuclear cells (MNC) by this drug. We measured intranuclear NFkappaB, total 
      cellular NFkappaB, inhibitor kappaB (IkappaB)alpha, reactive oxygen species (ROS) 
      generation, and p47(phox) subunit (a key component protein of nicotinamide 
      adenine dinucleotide phosphate oxidase) in MNC. Plasma tumor necrosis factor 
      (TNF)-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), monocyte 
      chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor type 1 
      (PAI-1), C-reactive protein (CRP), and interleukin (IL)-10 (antiinflammatory 
      cytokine) concentrations were also measured as mediators of inflammatory activity 
      that are regulated by the proinflammatory transcription factor NFkappaB. Seven 
      nondiabetic obese patients were given 400 mg troglitazone daily for 4 weeks. 
      Blood samples were collected before and at weekly intervals thereafter. MNC were 
      separated; and the levels of intranuclear NFkappaB, total cellular NFkappaB, 
      IkappaBalpha, and p47 (phox) subunit and ROS generation were determined. Plasma 
      was used to measure insulin glucose, TNFalpha, sICAM, MCP-1, PAI-1, CRP, and 
      IL-10. Plasma insulin concentrations fell significantly at week 1, from 31.2 +/- 
      29.1 to 14.2 +/- 11.4 mU/L (P < 0.01) and remained low throughout 4 weeks. Plasma 
      glucose concentrations did not alter significantly. There was a fall in 
      intranuclear NFkappaB, total cellular NFkappaB, and p47 (phox) subunit, with an 
      increase in cellular IkappaBalpha at week 2, which persisted until week 4. There 
      was a parallel fall in ROS generation by MNC at week 1; this progressed and 
      persisted until week 4 (P < 0.001). Plasma TNF-alpha, sICAM-1, MCP-1, and PAI-1 
      concentrations fell significantly at week 4. Plasma IL-10 concentration increased 
      significantly, whereas plasma CRP concentrations decreased. We conclude that 
      troglitazone has an antiinflammatory action that may contribute to its putative 
      antiatherosclerotic effects.
FAU - Ghanim, H
AU  - Ghanim H
AD  - Division of Endocrinology, Diabetes and Metabolism, State University of New York 
      at Buffalo, and Kaleida Health, Buffalo, New York 14209, USA.
FAU - Garg, R
AU  - Garg R
FAU - Aljada, A
AU  - Aljada A
FAU - Mohanty, P
AU  - Mohanty P
FAU - Kumbkarni, Y
AU  - Kumbkarni Y
FAU - Assian, E
AU  - Assian E
FAU - Hamouda, W
AU  - Hamouda W
FAU - Dandona, P
AU  - Dandona P
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromans)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Insulin)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoproteins)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 130068-27-8 (Interleukin-10)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Arteriosclerosis/*prevention & control
MH  - Blood Glucose/analysis
MH  - C-Reactive Protein/analysis
MH  - Cell Nucleus/chemistry
MH  - Chemokine CCL2/blood
MH  - Chromans/*pharmacology
MH  - Female
MH  - Humans
MH  - I-kappa B Proteins/blood/*physiology
MH  - Insulin/blood
MH  - Intercellular Adhesion Molecule-1/blood
MH  - Interleukin-10/blood
MH  - Leukocytes, Mononuclear/metabolism/ultrastructure
MH  - Male
MH  - Middle Aged
MH  - NADPH Oxidases
MH  - NF-kappa B/analysis/*antagonists & inhibitors
MH  - Obesity/*blood/complications
MH  - Phosphoproteins/blood
MH  - Plasminogen Activator Inhibitor 1/blood
MH  - Reactive Oxygen Species/metabolism
MH  - Thiazoles/*pharmacology
MH  - *Thiazolidinediones
MH  - Troglitazone
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 2001/03/10 10:00
MHDA- 2001/04/06 10:01
CRDT- 2001/03/10 10:00
PHST- 2001/03/10 10:00 [pubmed]
PHST- 2001/04/06 10:01 [medline]
PHST- 2001/03/10 10:00 [entrez]
AID - 10.1210/jcem.86.3.7309 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2001 Mar;86(3):1306-12. doi: 10.1210/jcem.86.3.7309.