| First Author | Van Lenten BJ | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 3 | Pages | 1923-9 |
| PubMed ID | 11034996 | Mgi Jnum | J:67047 |
| Mgi Id | MGI:1929786 | Doi | 10.1074/jbc.M004074200 |
| Citation | Van Lenten BJ, et al. (2001) Oxidized phospholipids induce changes in hepatic paraoxonase and ApoJ but not monocyte chemoattractant protein-1 via interleukin-6. J Biol Chem 276(3):1923-9 |
| abstractText | 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. |
