Nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is expressed in resting murine lymphocytes. The PPARalpha in T and B lymphocytes is both transactivation and transrepression competent.
Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear hormone receptor superfamily. PPARalpha and PPARgamma ligands have been demonstrated to exert anti-inflammatory activities in macrophages by repressing the activities of several transcription factors. PPARgamma 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 PPARalpha. PPARalpha represents the predominant isoform expressed in lymphocytes, whereas PPARgamma dominates in all cell types of the myeloid lineage. PPARalpha expression was down-regulated following T-cell activation while PPARgamma expression increased under the same activating conditions. PPARalpha expression in T cells may be regulated by microenvironmental factors, because Peyer's patch T cells expressed far greater levels of PPARalpha than T cells isolated from peripheral lymphoid organs. Exposure to specific ligand determined that PPARalpha in lymphocytes can effectively transactivate a peroxisome proliferator response element reporter construct. PPARalpha's ability to regulate endogenous genes, however, required treatment with histone deacetylase inhibitors. Finally, ligand activation of lymphocyte PPARalpha antagonized NF-kappaB. Our observation that a functional PPARalpha exists within T cells and B lymphocytes suggests an expanding role for this nuclear receptor in cells of the immune system.
Jones
Dallas C
DC
Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 84132, USA.
Ding
Xiaohong
X
Daynes
Raymond A
RA
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017930:Genes, Reporter; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010671:Phenylurea Compounds / Q000494:pharmacology; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D002087:Butyrates; D008024:Ligands; D010671:Phenylurea Compounds; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003907:Dexamethasone; D007371:Interferon-gamma; D008156:Luciferases; D006655:Histone Deacetylases; C121804:GW 9578