Human B Lymphocytes and B Lymphomas Express PPAR-γ and Are Killed by PPAR-γ Agonists

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2002-04, Vol.103 (1), p.22-33
• Main Authors: Padilla, Josué, Leung, Edmund, Phipps, Richard P.
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; apoptosis; Apoptosis - drug effects; B lymphocytes; B-Lymphocytes - drug effects; B-Lymphocytes - physiology; Biological and medical sciences; Chemotherapy; Humans; Immunohistochemistry; lipid mediators; Medical sciences; Pharmacology. Drug treatments; PPAR-γ; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - pharmacology; Receptors, Cytoplasmic and Nuclear - analysis; Receptors, Cytoplasmic and Nuclear - physiology; Transcription Factors - analysis; Transcription Factors - physiology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.2001.5181

This paper evaluates the expression and functional significance of PPAR-γ on human B cells. Recent interest in PPAR-γ has focused on its adipogenic effects on non-bone marrow-derived cells. PPAR-γ agonists also have been proposed as anti-inflammatory agents owing to inhibition of NF-κB activation. We report herein the first study evaluating PPAR-γ 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-γ protein as determined by immunocytochemistry. The expression of 80-kDa PPAR-γ on human B lymphocytes and B lymphomas was confirmed by Western blot analysis. 15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2), a natural PPAR-γ agonist, has a dose-dependent antiproliferative and cytotoxic effect on normal and malignant B cells as shown by [3H]thymidine and MTT assays. Only PPAR-γ agonists (thiazolidinediones) and not PPAR-α agonists mimicked the effect of 15d-PGJ2 on B lineage cells, indicating that the mechanism by which 15d-PGJ2 negatively affects B lineage cells involves, in part, PPAR-γ. The mechanism whereby PPAR-γ 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-γ expression and its significance on human B lymphocytes. PPAR-γ agonists may serve as a counterbalance to the stimulating effects of other prostaglandins, namely PGE2, which promotes B cell immunoglobulin class switching. Finally, the use of prostaglandins such as 15d-PGJ2 and synthetic PPAR-γ agonists to induce apoptosis in B lineage cells may lead to the development of novel therapies for potentially fatal B lymphomas.