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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: Padilla, Josue; Leung, Edmund; Phipps, Richard P

Published In Clin Immunol, (2002 Apr)

Abstract: 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.

PubMed ID: 11987982 Exiting the NIEHS site

MeSH Terms: Apoptosis/drug effects; B-Lymphocytes/drug effects*; B-Lymphocytes/physiology; Humans; Immunohistochemistry; Prostaglandin D2/analogs & derivatives*; Prostaglandin D2/pharmacology*; Receptors, Cytoplasmic and Nuclear/analysis; Receptors, Cytoplasmic and Nuclear/physiology*; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Transcription Factors/analysis; Transcription Factors/physiology*

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