Human B lymphocytes and B lymphomas express PPAR-gamma and are killed by PPAR-gamma agonists

This paper evaluates the expression and functional significance of PPAR-gamma on human B cells. Recent interest in PPAR-gamma has focused on its adipogenic effects on non-bone marrow-derived cells. PPAR-gamma agonists also have been proposed as anti-inflammatory agents owing to inhibition of NF-kapp...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 103(2002), 1 vom: 30. Apr., Seite 22-33
1. Verfasser: Padilla, Josué (VerfasserIn)
Weitere Verfasser: Leung, Edmund, Phipps, Richard P
Format: Aufsatz
Sprache:English
Veröffentlicht: 2002
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 15-deoxy-delta(12,14)-prostaglandin J2 Receptors, Cytoplasmic and Nuclear Transcription Factors Prostaglandin D2 RXY07S6CZ2
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520 |a This paper evaluates the expression and functional significance of PPAR-gamma on human B cells. Recent interest in PPAR-gamma has focused on its adipogenic effects on non-bone marrow-derived cells. PPAR-gamma agonists also have been proposed as anti-inflammatory agents owing to inhibition of NF-kappa B activation. We report herein the first study evaluating PPAR-gamma expression and functional significance in human B lineage cells. Interestingly, normal human B cells and a variety of B lymphoma cells (e.g., Daudi, Ramos, and Raji) express PPAR-gamma protein as determined by immunocytochemistry. The expression of 80-kDa PPAR-gamma on human B lymphocytes and B lymphomas was confirmed by Western blot analysis. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), a natural PPAR-gamma agonist, has a dose-dependent antiproliferative and cytotoxic effect on normal and malignant B cells as shown by [(3)H]thymidine and MTT assays. Only PPAR-gamma agonists (thiazolidinediones) and not PPAR-alpha agonists mimicked the effect of 15d-PGJ(2) on B lineage cells, indicating that the mechanism by which 15d-PGJ(2) negatively affects B lineage cells involves, in part, PPAR-gamma. The mechanism whereby PPAR-gamma agonists induce cytotoxicity is via apoptosis as shown by Annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL assay. This is the first study evaluating PPAR-gamma expression and its significance on human B lymphocytes. PPAR-gamma agonists may serve as a counterbalance to the stimulating effects of other prostaglandins, namely PGE(2), which promotes B cell immunoglobulin class switching. Finally, the use of prostaglandins such as 15d-PGJ(2) and synthetic PPAR-gamma agonists to induce apoptosis in B lineage cells may lead to the development of novel therapies for potentially fatal B lymphomas 
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650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Research Support, U.S. Gov't, P.H.S. 
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700 1 |a Leung, Edmund  |e verfasserin  |4 aut 
700 1 |a Phipps, Richard P  |e verfasserin  |4 aut 
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