Interleukin-6 is critical to the short-term, but not long-term, regulation of paraoxonase and apoJ by oxidized phospholipids, and is not required for OXPL regulation of MCP-1.
Does IL-6 mediate the effects of oxidized phospholipids on paraoxonase, apoJ, and MCP-1?
IL-6 is critical for the short-term but not long-term regulation of paraoxonase by oxidized phospholipids, and is not required for OXPL-induced regulation of MCP-1.
In this study, we tested if interleukin-6 (IL-6) plays a role in mediating the effects of oxidized phospholipids (OXPL). Treatment of HepG2 cells with oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphoryl choline (OX-PAPC), or biologically active lipids present in mildly oxidized low density lipoprotein, increased apolipoprotein J (apoJ), and decreased paraoxonase (PON) mRNA levels. Antibodies to IL-6 blocked these changes. IL-6 treatment in the absence of OXPL produced the same pattern of mRNA changes observed with OXPL treatment alone. In vivo, OX-PAPC injected into C57BL/6J mice resulted in a marked reduction in PON activity and an increase in apoJ levels in plasma after 16 h. Injection of OX-PAPC into IL-6-deficient C57BL/6J mice (IL-6 -/-) did not alter either PON activity or apoJ levels. We then tested if other mechanisms involved in fatty streak formation depended upon IL-6. Antibody to IL-6 had no effect on OX-PAPC-induced secretion of MCP-1 by endothelial cells nor on MCP-1 mRNA expression in HepG2 cells. C57BL/6J and IL-6 -/- mice fed an atherogenic diet both demonstrated markedly reduced plasma PON activities and the IL-6 -/- mice developed fatty streaks to a greater degree than wild-type mice. We conclude that IL-6 is critical to short term but not long term regulation of PON and that IL-6 is not required for OXPL regulation of MCP-1.
Lenten et al. (Mon,) conducted a other in Atherosclerosis. Oxidized phospholipids (OX-PAPC) and IL-6 deficiency/antibodies vs. Wild-type mice / absence of OXPL was evaluated on Changes in hepatic paraoxonase (PON) and apoJ levels, and MCP-1 expression. Interleukin-6 is critical to the short-term, but not long-term, regulation of paraoxonase and apoJ by oxidized phospholipids, and is not required for OXPL regulation of MCP-1.