The modulatory mechanisms of fenofibrate on human primary T cells.
Fenofibrate is a lipid-lowering agent and supposed to have anti-inflammatory properties. But it was rarely evaluated for the signal transduction on human primary T cells. Therefore, the methods including enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility shift assay, luciferase assay and Western blotting were used to investigate the mechanisms of fenofibrate on human primary T cells, isolated from normal human beings. We found that fenofibrate could dose-dependently inhibit cytokine production such as interleukin-2, interleukin-4, tumor necrosis factor-alpha and interferon-gamma from activated T cells. Also, it could down-regulate activator protein-1 (AP-1) DNA-binding activities in T cells. As performing in vivo study, fenofibrate reduced the AP-1 transcriptional activity in Jurkat cells. Finally, fenofibrate inhibited the activation of c-Jun NH2-terminal protein kinase and P38 mitogen-activated protein kinase. These results may extend potential therapeutic mechanisms of fenofibrate on cardiovascular disease with inflammatory processes.
Cheng
Shu-Meng
SM
Division of Cardiology, Tri-Service General Hospital, Nation Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, ROC. chengsm@cm1.hinet.net
Chu
Kai-Min
KM
Lai
Jenn-Haung
JH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009994:Osmolar Concentration; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D011345:Fenofibrate