The effects of oxidized low density lipoproteins on inducible mouse macrophage gene expression are gene and stimulus dependent

The Journal of Clinical Investigation
T A HamiltonG M Chisolm

Abstract

Oxidized LDL has been previously reported to suppress the expression of genes induced in mononuclear phagocytes by inflammatory stimuli. In this study we extend these findings to demonstrate that the suppressive effects of oxidized LDL vary depending upon the gene being monitored and the stimulus being used to induce or enhance its expression. The expression of a selection of LPS-inducible genes exhibited differential sensitivity to pretreatment with oxidized LDL. Furthermore, the ability of oxidized LDL to suppress gene expression varied markedly with the inducing stimulus used. TNF alpha and IP-10 mRNA expression induced by IFN gamma and IL-2 was markedly more sensitive to suppression by oxidized LDL than that induced by LPS. The cooperative effects of IFN gamma and LPS on the expression of the inducible nitric oxide synthase gene were suppressed by oxidized LDL while the antagonistic effect of IFN gamma on LPS-induced expression of the TNF receptor type II mRNA was not altered. The suppressive activity of LDL was acquired only after extensive oxidation and was localized in the extractable lipid component. These results suggest a potent and direct connection between the oxidative modification of LDL and the chronic inflammati...Continue Reading

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Citations

Nov 24, 1999·Biochemical and Biophysical Research Communications·M K JangY B Park
Jan 1, 1996·Free Radical Biology & Medicine·J A Berliner, J W Heinecke
May 24, 2003·Biochemical and Biophysical Research Communications·Rocio Aguilar-Gaytan, Jaime Mas-Oliva
Apr 28, 1999·Free Radical Biology & Medicine·A HuangW L Stone
Oct 9, 2012·The Journal of Clinical Investigation·Maliheh Nazari-JahantighAndreas Schober
Jul 17, 2012·Journal of Clinical Biochemistry and Nutrition·Hiroyuki Itabe
Dec 21, 2006·Archives of Physiology and Biochemistry·Felicia Antohe
May 25, 2007·Clinica Chimica Acta; International Journal of Clinical Chemistry·Blai CollJorge Joven
Sep 24, 2004·Biochemical and Biophysical Research Communications·Moon Kyoo JangYong Bok Park
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Feb 17, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·M P de WintherM H Hofker
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Sep 27, 2002·Prostaglandins, Leukotrienes, and Essential Fatty Acids·C BanfiE Tremoli

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