Abstract
The peroxisome-proliferator activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily of ligand activated transcription factors, plays a key role in the anti-diabetic actions of the thiazolidinediones (TZDs). PPARgamma induces the expression of many genes involved in lipid anabolism, including the adipocyte fatty acid binding protein (aP2), and is a key regulator of adipocyte differentiation. PPARgamma is also expressed in hematopoietic cells and is up-regulated in activated monocytes/macrophages. Activation of PPARgamma may play a role in the induction of differentiation of macrophages to foam cells that are associated with atherosclerotic lesions. We report that both natural and synthetic PPARgamma agonists induce time- and dose-dependent increases in aP2 mRNA in both primary human monocytes and the monocytic cell line, THP-1. These data suggest that PPARgamma activation may play a role in monocyte differentiation and function analogous to its well-characterized role in adipocytes.
Copyright 1999 Academic Press.
MeSH terms
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Adipocytes / metabolism*
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Carrier Proteins / genetics*
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Cell Differentiation / drug effects
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Cell Line
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Cells, Cultured
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Chromans / pharmacology
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins
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Fatty Acids / metabolism*
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Gene Expression / drug effects
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Humans
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Kinetics
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Monocytes / cytology
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Monocytes / drug effects
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Monocytes / metabolism*
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Myelin P2 Protein / genetics*
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Neoplasm Proteins*
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Prostaglandin D2 / analogs & derivatives
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Prostaglandin D2 / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / agonists
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Rosiglitazone
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Tetradecanoylphorbol Acetate / pharmacology
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Thiazoles / pharmacology
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Thiazolidinediones*
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Transcription Factors / agonists
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Transcription Factors / metabolism*
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Troglitazone
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Tumor Suppressor Proteins*
Substances
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15-deoxy-delta(12,14)-prostaglandin J2
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Carrier Proteins
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Chromans
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FABP7 protein, human
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins
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Fatty Acids
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Myelin P2 Protein
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Neoplasm Proteins
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Thiazoles
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Thiazolidinediones
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Transcription Factors
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Tumor Suppressor Proteins
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Rosiglitazone
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Troglitazone
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Tetradecanoylphorbol Acetate
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Prostaglandin D2