Agonists of PPAR-alpha, PPAR-gamma, and RXR inhibit the formation of foam cells from macrophages in mice with inflammation.
We studied the effect of agonists of peroxisome proliferator-activated receptors alpha and gamma and retinoid X receptors on the concentration and synthesis of lipids in macrophages of C57B1/6 mice with inflammation induced by intraperitoneal injection of zymosan. We revealed a significant increase in [1-14C]oleate incorporation into cholesterol esters and triglycerides, increase in the content of free cholesterol, cholesterol esters, and triglycerides, and formation of oil red-stained lipid inclusions in peritoneal macrophages 24 h after administration of zymosan in a dose of 50 mg/kg. Treatment with agonists of retinoid X receptors and peroxisome proliferator-activated receptors alpha and gamma 30 min before and 12 h after zymosan injection decreased the synthesis of triglycerides and cholesterol esters, reduced the content of free cholesterol, cholesterol esters, and triglycerides in macrophages, and prevented the formation of cytoplasmic lipid inclusions in macrophage-derived foam cells during inflammation.
Dushkin
M I
MI
Institute of Clinical Immunology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk. midushkin@soramn.ru
Khoshchenko
O M
OM
Posokhova
E N
EN
Schvarts
Y Sh
YSh
D000077556:Alitretinoin; D000818:Animals; D001629:Bezafibrate / Q000008:administration & dosage / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists* / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015054:Zymosan
D002788:Cholesterol Esters; D047493:PPAR alpha; D047495:PPAR gamma; D047488:Retinoid X Receptors; D045162:Thiazolidinediones; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D000077556:Alitretinoin; D014212:Tretinoin; D015054:Zymosan; D002784:Cholesterol; D001629:Bezafibrate