Comparison of PPARδ and PPARγ in inhibiting the pro-inflammatory effects of C-reactive protein in endothelial cells.
BACKGROUND
Inflammation associated with endothelial cell dysfunction is a key step of atherogenesis. C-reactive protein (CRP), used to serve as a nonspecific clinical inflammation marker, has now emerged as a new marker for cardiovascular diseases. Recently, PPARδ has revealed benefits for dealing with inflammation. The relationship between CRP-induced inflammation and PPARδ agonist remains unclear.


METHODS
Human umbilical vein endothelial cells (HUVECs) were separated into the following groups: 25 μg CRP alone for 15 hours; CRP-treated with 1 μM PPARδ(L-165041) or 10 μM PPARγ(troglitazone) agonists, and untreated HUVECs. This research focused on the CRP underlying signaling pathways and the effects of PPAR agonists on monocyte attachment to endothelial cells.


RESULTS
Levels of interleukin-6 (IL-6) and IL-8 increased by CRP were both significantly attenuated by pretreatment with PPARδ or PPARγ agonists, but the needed dose of PPARδ to reach the same effect was less than PPARγ agonist. After incubation with CRP, immunoblotting showed a significant increase in NF-κB activation and CD32 receptor. These changes were associated with a significant increase of MCP-1 and VCAM-1 expression. PPARδ treatment not only decreased these pro-inflammatory effects in HUVECs but also significantly attenuated monocyte adhesion to endothelial cells in less dosage than PPARγ.


CONCLUSIONS
The results suggest that PPARδ attenuated CRP-induced pro-inflammatory effects may through CD32 and NF-κB pathway. PPARδ may serve as a more potent therapeutic target than PPARγ in atherosclerosis or inflammatory therapy.
Liang
Yao-Jen
YJ
Department and Institute of Life Science, Fu-Jen Catholic University, and Department of Medical Education and REsearch, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Liu
Yuan-Chun
YC
Chen
Chao-Yi
CY
Lai
Ling-Ping
LP
Shyu
Kou-Gi
KG
Juang
Shiow-Jen
SJ
Wang
Bao-Wei
BW
Leu
Jyh Gang
JG
D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism; D002097:C-Reactive Protein / Q000276:immunology* / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism
C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D047494:PPAR delta; D047495:PPAR gamma; D017452:Receptors, IgG; D002097:C-Reactive Protein