The 2-series prostaglandins suppress VLDL secretion in an inflammatory condition-dependent manner in primary rat hepatocytes.
In the liver, prostaglandins (PG) generated mainly by activated non-parenchymal cells can modulate the parenchymal cell function during homeostasis and inflammation. Whether prostaglandins regulate the hepatocyte VLDL assembling/secretor phenotype in both conditions remains unresolved. We sought to determine whether and how PGE2, PGD2, and PGF2alpha (5 and 50 microM) have a role in VLDL secretion regulation in resting and interleukin-6 (IL-6) stimulated rat hepatocytes. Prostaglandins led to comparable, concentration-dependent reductions in the secretion of VLDL apoB and lipids by resting, 24 h-cultured cells. Moreover, each apoB copy recruited less of each lipid class, correlating with reduced particle size, lipogenesis and cholesterogenesis, and impaired cellular triacylglycerol recycling. Triacylglycerol output reduction occurred early, as the transient PGD2- and PGF2alpha -promoted apoB mRNA decreases. IL-6 markedly increased the apoB mRNA expression and the secretion of its protein in triacylglycerol-poor VLDL. The latter was uniquely blunted by PGE2, which unaffected basal or IL-6-activated apoB gene expression. Collectively, our findings show inflammation condition-based roles for 2-series-prostaglandins in VLDL secretion modulation. Whereas in non-stimulated hepatocytes, they all inhibited VLDL-apoB output, interfered with lipid provision for lipoprotein assembly and may be regarded as pro-steatotic, the anti-inflammatory PGE2 antagonized the IL-6-promoted VLDL secretion contributing in restoring liver homeostasis.
Department of Physiology, University of the Basque Country Medical School, P.O. Box 699, 48080-Bilbao, Spain.
Silvia
S
Pérez
Patricia
P
Aspichueta
Begoña
B
Ochoa
Yolanda
Y
Chico
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D001055:Apolipoproteins B; D002352:Carrier Proteins; D015850:Interleukin-6; D008079:Lipoproteins, VLDL; D011453:Prostaglandins; D012333:RNA, Messenger; C106092:microsomal triglyceride transfer protein; D015237:Dinoprost; D064429:Fatty Acid Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2