Inflammation stimulates the expression of PCSK9.
Inflammation induces marked changes in lipid and lipoprotein metabolism. Proprotein convertase subtilisin kexin 9 (PCSK9) plays an important role in regulating LDL receptor degradation. Here, we demonstrate that LPS decreases hepatic LDL receptor protein but at the same time hepatic LDL receptor mRNA levels are not decreased. We therefore explored the effect of LPS on PCSK9 expression. LPS results in a marked increase in hepatic PCSK9 mRNA levels (4h 2.5-fold increase; 38h 12.5-fold increase). The increase in PCSK9 is a sensitive response with 1microg LPS inducing a (1/2) maximal response. LPS also increased PCSK9 expression in the kidney. Finally, zymosan and turpentine, other treatments that induce inflammation, also stimulated hepatic expression of PCSK9. Thus, inflammation stimulates PCSK9 expression leading to increased LDL receptor degradation and decreasing LDL receptors thereby increasing serum LDL, which could have beneficial effects on host defense.
Feingold
Kenneth R
KR
Metabolism Section (111F), Department of Veterans Affairs Medical Center, 4150 Clement Street, University of California San Francisco, San Francisco, CA 94121, USA. kenneth.feingold@ucsf.edu
Moser
Arthur H
AH
Shigenaga
Judy K
JK
Patzek
Sophie M
SM
Grunfeld
Carl
C
D000818:Animals; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D007509:Irritants / Q000633:toxicity; D007668:Kidney / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011973:Receptors, LDL / Q000097:blood / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D014425:Turpentine / Q000633:toxicity; D015054:Zymosan / Q000633:toxicity
D007509:Irritants; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011973:Receptors, LDL; D015054:Zymosan; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D014425:Turpentine