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Oxidized LDL-induced JAB1 influences NF-κB independent inflammatory signaling in human macrophages during foam cell formation.

Journal of biomedical science (2017-02-09)
Anja Schwarz, Gabriel A Bonaterra, Hans Schwarzbach, Ralf Kinscherf
RÉSUMÉ

Oxidized low-density lipoprotein (oxLDL) mediates the transformation of macrophages (MΦ) to cholesterol-rich foam cells and the release of pro-inflammatory cytokines during atherogenesis. JAB1 (Jun activation domain binding protein-1) is present in all stages of human plaques, involved in the Toll-like receptor-mediated activation of p38 mitogen-activated protein kinase (MAPK) and controls nuclear factor-kappa B (NF-κB) activation. Thus, we were interested in the role of JAB1 during foam cell formation of MΦ after oxLDL exposition. We found that JAB1 was present in CD68-immunoreactive (-ir) MΦ in atherosclerotic plaques of apolipoprotein E knockout (ApoE We demonstrate that oxLDL induces JAB1 expression and influences its cellular localization, whereby the p38 MAPK signaling pathway is modified with consequences for inflammation of human MΦ in foam cells and atherosclerotic lesions.

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MISSION® esiRNA, targeting human COPS5