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Prostaglandin D 2 , its metabolite 15‐d‐PGJ 2 , and peroxisome proliferator activated receptor‐γ agonists induce apoptosis in transformed, but not normal, human T lineage cells
Author(s) -
Harris Sarah G.,
Phipps Richard P.
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.0019-2805.2001.01340.x
Subject(s) - prostaglandin d2 , troglitazone , receptor , biology , apoptosis , prostaglandin , peroxisome proliferator activated receptor , microbiology and biotechnology , ciglitazone , metabolite , jurkat cells , peroxisome proliferator activated receptor gamma , endocrinology , biochemistry , immunology , t cell , immune system
Summary Prostaglandin D 2 (PGD 2 ) is abundantly produced by mast cells, platelets, and alveolar macrophages and has been proposed as a key immunoregulatory lipid mediator. 15‐Deoxy‐Δ 12,14 ‐PGJ 2 (15‐d‐PGJ 2 ), a key PGD 2 metabolite, is under intense study as a potential anti‐inflammatory mediator. Little is known about PGD 2 or the role of 15‐d‐PGJ 2 , if any, in regulating the activities of human T lineage cells. In this report we demonstrate that both PGD 2 and 15‐d‐PGJ 2 have potent antiproliferative effects, and in fact kill human T lymphocyte lines derived from malignant cells by an apoptotic mechanism. Interestingly, normal human T cells were not similarly affected. Although the T lymphocyte lines express mRNA for the PGD 2 receptor (DP‐R), a potent DP receptor agonist, BW245C, did not inhibit the proliferation or viability of the cells, suggesting an alternative mechanism of action. PGD 2 and 15‐d‐PGJ 2 can bind to the peroxisome proliferator activated receptor‐γ (PPAR‐γ) which is implicated in lipid metabolism and apoptosis. Exposure to synthetic PPAR‐γ ligands (e.g. ciglitazone, troglitazone) mimicked the inhibitory responses of PGD 2 and 15‐d‐PGJ 2 , and induced apoptosis in the transformed T cells consistent with a PPAR‐γ‐dependent mechanism. These observations suggest that PPAR‐γ ligands (which may include PGD 2 ) provide strong apoptotic signals to transformed, but not normal T lymphocytes. Thus, the efficacy of utilizing PPAR‐γ and its ligands as therapeutics for human T cell cancers needs to be further evaluated.