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National Institute of Environmental Health Sciences

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Publication Detail

Title: Activated human T lymphocytes express cyclooxygenase-2 and produce proadipogenic prostaglandins that drive human orbital fibroblast differentiation to adipocytes.

Authors: Feldon, Steven E; O'loughlin, Charles W; Ray, Denise M; Landskroner-Eiger, Shira; Seweryniak, Kathryn E; Phipps, Richard P

Published In Am J Pathol, (2006 Oct)

Abstract: The differentiation of preadipocyte fibroblasts to adipocytes is a crucial process to many disease states including obesity, cardiovascular, and autoimmune diseases. In Graves' disease, the orbit of the eye can become severely inflamed and infiltrated with T lymphocytes as part of the autoimmune process. The orbital fibroblasts convert to fat-like cells causing the eye to protrude, which is disfiguring and can lead to blindness. Recently, the transcription factor peroxisome proliferator activated receptor (PPAR)-gamma and its natural (15d-PGJ2) and synthetic (thiazolidinedione-type) PPAR-gamma agonists have been shown to be crucial to the in vitro differentiation of preadipocyte fibroblasts to adipocytes. We show herein several novel findings. First, that activated T lymphocytes from Graves' patients drive the differentiation of PPAR-gamma-expressing orbital fibroblasts to adipocytes. Second, this adipogenic differentiation is blocked by nonselective small molecule cyclooxygenase (Cox)-1/Cox-2 inhibitors and by Cox-2 selective inhibitors. Third, activated, but not naive, human T cells highly express Cox-2 and synthesize prostaglandin D2 and related prostaglandins that are PPAR-gamma ligands. These provocative new findings provide evidence for how activated T lymphocytes, through production of PPAR-gamma ligands, profoundly influence human fibroblast differentiation to adipocytes. They also suggest the possibility that, in addition to the orbit, T lymphocytes influence the deposition of fat in other tissues.

PubMed ID: 17003477 Exiting the NIEHS site

MeSH Terms: Adipocytes/cytology*; Adipogenesis*; Cell Differentiation*; Coculture Techniques; Cyclooxygenase 2/metabolism*; Fibroblasts/cytology; Fibroblasts/metabolism; Graves Disease/enzymology; Humans; Ligands; Lymphocyte Activation; Membrane Proteins/metabolism*; Orbit/cytology*; PPAR gamma/agonists; PPAR gamma/metabolism; Prostaglandin D2/analogs & derivatives; Prostaglandin D2/biosynthesis; Prostaglandin D2/pharmacology; Prostaglandins/biosynthesis*; T-Lymphocytes/enzymology*; T-Lymphocytes/metabolism

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