Specific immunization strategies against oxidized low-density lipoprotein: a novel way to reduce nonalcoholic steatohepatitis in mice.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Veerle BieghsRonit Shiri-Sverdlov

Abstract

Nonalcoholic steatohepatitis (NASH) is characterized by hepatic lipid accumulation combined with inflammation, which can ultimately progress into cirrhosis. Recently, we demonstrated that deletion of scavenger receptors (SRs) CD36 and SR-A in hematopoietic cells reduced hepatic inflammation. In addition to uptake of modified lipoproteins, CD36 and SR-A are also involved in other functions that can activate the inflammatory response. Therefore, the actual trigger for SR activation during NASH is unclear. Here, we hypothesized that hepatic inflammation is triggered by recognition of oxidized LDL (oxLDL) by Kupffer cells (KCs). To inhibit recognition of oxLDL by KCs, low-density lipoprotein receptor (Ldlr(-/-) ) mice were immunized with heat-inactivated pneumococci, which were shown to induce the production of anti-oxLDL immunoglobulin M (IgM) antibodies, due to molecular mimicry with oxLDL. The mice received a high-fat, high-cholesterol diet during the last 3 weeks to induce NASH. Immunization with pneumococci increased anti-oxLDL IgM levels and led to a reduction in hepatic inflammation, as shown by reduced macrophage, neutrophil, and T cell infiltration, and reduced gene expression of tumor necrosis factor (Tnf), interleukin-6 ...Continue Reading

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Citations

May 15, 2013·Trends in Immunology·Veerle Bieghs, Christian Trautwein
Mar 26, 2016·The Journal of Nutritional Biochemistry·Yu-Sheng LaiShao-Chun Lu
Sep 26, 2015·International Journal of Molecular Sciences·Sofie M A WalenberghRonit Shiri-Sverdlov
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