Nuclear Receptor Peroxisome Proliferator-activated Receptor α (PPARα) Is Expressed in Resting Murine Lymphocytes
THE PPARα IN T AND B LYMPHOCYTES IS BOTH TRANSACTIVATION AND TRANSREPRESSION COMPETENT*
- From the ‡Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132 and the¶Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah 84112
Abstract
Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear hormone receptor superfamily. PPARα and PPARγ ligands have been demonstrated to exert anti-inflammatory activities in macrophages by repressing the activities of several transcription factors. PPARγ is expressed in T lymphocytes and may play a role in cytokine production, cellular proliferation, and susceptibility to apoptosis. Herein, we demonstrate that T and B lymphocytes constitutively express PPARα. PPARα represents the predominant isoform expressed in lymphocytes, whereas PPARγ dominates in all cell types of the myeloid lineage. PPARα expression was down-regulated following T-cell activation while PPARγ expression increased under the same activating conditions. PPARα expression in T cells may be regulated by microenvironmental factors, because Peyer's patch T cells expressed far greater levels of PPARα than T cells isolated from peripheral lymphoid organs. Exposure to specific ligand determined that PPARα in lymphocytes can effectively transactivate a peroxisome proliferator response element reporter construct. PPARα's ability to regulate endogenous genes, however, required treatment with histone deacetylase inhibitors. Finally, ligand activation of lymphocyte PPARα antagonized NF-κB. Our observation that a functional PPARα exists within T cells and B lymphocytes suggests an expanding role for this nuclear receptor in cells of the immune system.
Footnotes
-
↵* This work was supported in part by National Institutes of Health Grants CA25917 and DK55491, by a Browning Foundation grant, and by Department of Veteran's Affairs Medical Research Funds.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵§ Supported by DHHS/NIDDK, National Institutes of Health, Hematology Research Training Grant T32 DK07115.
-
↵‖ To whom correspondence should be addressed: Dept. of Pathology, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132-2501. Tel.: 801-581-3013; Fax: 801-581-8946; E-mail: daynes.office@path.utah.edu.
-
Published, JBC Papers in Press, November 28, 2001, DOI 10.1074/jbc.M106908200
-
↵2 Jones, D. C., Ding, X., Zhang, T., and Daynes, R. A., manuscript in preparation.
- Abbreviations:
- PPAR
-
peroxisome proliferator-activated receptor
- Aco
-
acyl-CoA oxidase
- CPT-1
-
carnitine palmitoyl transferase-1
- Dex
-
dexamethasone
- EMSA
-
electrophoretic mobility shift assay
- HDAC
-
histone deacetylase
- NF-κB
-
nuclear factor κB
- PLN
-
peripheral lymph node
- PMSF
-
phenylmethylsulfonyl fluoride
- PP
-
Peyer's patch
- PPRE
-
peroxisome proliferator response element
- PR
-
progesterone receptor
- TSA
-
trichostatin A
- STAT
-
signal transducers and activators of transcription
- FCS
-
fetal calf serum
- FITC
-
fluorescein isothiocyanate
- DTT
-
dithiothreitol
- TBS
-
Tris-buffered saline
- ELISA
-
enzyme-linked immunosorbent assay
- IL-6
-
interleukin-6
- PMA
-
phorbol 12-myristate 13-acetate
- PHA
-
phytohemagglutinin
- IFN-γ
-
interferon γ
-
- Received July 20, 2001.
- Revision received October 23, 2001.
- The American Society for Biochemistry and Molecular Biology, Inc.
