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- Title
PPAR-γ-Mediated Regulation of Normal and Malignant B Lineage Cells.
- Authors
PADILLA, JOSUÉ; KAUR, KULJEET; HARRIS, SARAH G.; PHIPPS, RICHARD P.
- Abstract
A bstract: Prostaglandins of the E-series stimulate B lymphocytes by enhancing immunoglobulin-class switching and antibody production. Little is known about whether or not other prostaglandins affect B lineage cells and perhaps counterbalance the stimulatory effects of PGE2. PGD2 is a major product of cyclooxygenase in bone marrow and in macrophages, suggesting a role for this lipid product in immunological responses. PGD2 undergoes dehydration to the biologically active prostaglandin 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) that binds to the nuclear receptor known as peroxisome proliferator-activated receptor gamma (PPAR-γ). We found that normal mouse B cells and a Wvariety of B lymphoma cells (e.g., 70Z/3, WEHI-231, CH12, and J558) express PPAR-γmRNA and the 67-kDa PPAR-γ protein. 15d-PGJ2 had a dose-dependent antiproliferative/cytotoxic effect on normal and malignant B cells, as shown by 3H-thymidine and MTT assays. Only PPAR-γ agonists (i.e., thiazolidinediones) mimicked the effect of 15d-PGJ2 on B lineage cells, indicating that the mechanism by which 15d-PGJ2 negatively affects B lineage cells involves PPAR-γ. The mechanism whereby PPAR-γ agonists induced cytotoxicity is via apoptosis, as shown by Annexin V assays. PPAR-γ agonists may serve as a counterbalance to the stimulating effects of PGE2, which promotes B-cell differentiation. 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 therapies for fatal PGE2-resistant B lymphomas.
- Publication
Annals of the New York Academy of Sciences, 2000, Vol 905, Issue 1, p97
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.2000.tb06542.x