Journal
CLINICAL IMMUNOLOGY
Volume 103, Issue 1, Pages 22-33Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/clim.2001.5181
Keywords
PPAR-gamma; B lymphocytes; apoptosis; lipid mediators
Categories
Funding
- NCI NIH HHS [CA11198] Funding Source: Medline
- NEI NIH HHS [EY11708] Funding Source: Medline
- NHLBI NIH HHS [T32HL07949-01, HL56002] Funding Source: Medline
- NIDCR NIH HHS [DE11390, 5-T32DE07061-21] Funding Source: Medline
- NIEHS NIH HHS [ES01247] Funding Source: Medline
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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-kappaB 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 anti-proliferative and cytotoxic effect on normal and malignant B cells as shown by [H-3]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. (C) 2002 Elsevier Science (USA).
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