TY - JOUR
T1 - Peroxisome Proliferator-Activated Receptor α Agonists as Therapy for Autoimmune Disease
AU - Lovett-Racke, Amy E.
AU - Hussain, Rehana Z.
AU - Northrop, Sara
AU - Choy, Judy
AU - Rocchini, Anne
AU - Matthes, Lela
AU - Chavis, Janet A.
AU - Diab, Asim
AU - Drew, Paul D.
AU - Racke, Michael K.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2004/5/1
Y1 - 2004/5/1
N2 - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ ligands, which include the naturally occurring PG metabolite 15-deoxy-Δ12,14-PGJ 2 (15d-PGJ2), as well as thiazolidinediones, have been shown to have anti-inflammatory activity. The PPARα agonists, gemfibrozil, ciprofibrate, and fenofibrate, have an excellent track history as oral agents used to treat hypertriglyceridemia. In the present study, we demonstrate that these PPARα agonists can increase the production of the Th2 cytokine, IL-4, and suppress proliferation by TCR transgenic T cells specific for the myelin basic protein Ac1-11, as well as reduce NO production by microglia. Oral administration of gemfibrozil and fenofibrate inhibited clinical signs of experimental autoimmune encephalomyelitis. More importantly, gemfibrozil was shown to shift the cytokine secretion of human T cell lines by inhibiting IFN-γ and promoting IL-4 secretion. These results suggest that PPARα agonists such as gemfibrozil and fenofibrate, may be attractive candidates for use in human inflammatory conditions such as multiple sclerosis.
AB - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ ligands, which include the naturally occurring PG metabolite 15-deoxy-Δ12,14-PGJ 2 (15d-PGJ2), as well as thiazolidinediones, have been shown to have anti-inflammatory activity. The PPARα agonists, gemfibrozil, ciprofibrate, and fenofibrate, have an excellent track history as oral agents used to treat hypertriglyceridemia. In the present study, we demonstrate that these PPARα agonists can increase the production of the Th2 cytokine, IL-4, and suppress proliferation by TCR transgenic T cells specific for the myelin basic protein Ac1-11, as well as reduce NO production by microglia. Oral administration of gemfibrozil and fenofibrate inhibited clinical signs of experimental autoimmune encephalomyelitis. More importantly, gemfibrozil was shown to shift the cytokine secretion of human T cell lines by inhibiting IFN-γ and promoting IL-4 secretion. These results suggest that PPARα agonists such as gemfibrozil and fenofibrate, may be attractive candidates for use in human inflammatory conditions such as multiple sclerosis.
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U2 - 10.4049/jimmunol.172.9.5790
DO - 10.4049/jimmunol.172.9.5790
M3 - Article
C2 - 15100326
AN - SCOPUS:11144357288
SN - 0022-1767
VL - 172
SP - 5790
EP - 5798
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -