4.6 Article

High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation

Journal

IMMUNOLOGY
Volume 149, Issue 3, Pages 306-319

Publisher

WILEY
DOI: 10.1111/imm.12638

Keywords

apolipoprotein A I; high-density lipoprotein; inflammasome; interleukin-1 beta

Categories

Funding

  1. National Heart, Lung, and Blood Institute

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Interleukin-1 beta (IL-1 beta), a potent pro-inflammatory cytokine, has been implicated in many diseases, including atherosclerosis. Activation of IL-1 beta is controlled by a multi-protein complex, the inflammasome. The exact initiating event in atherosclerosis is unknown, but recent work has demonstrated that cholesterol crystals (CC) may promote atherosclerosis development by activation of the inflammasome. High-density lipoprotein (HDL) has consistently been shown to be anti-atherogenic and to have anti-inflammatory effects, but its mechanism of action is unclear. We demonstrate here that HDL is able to suppress IL-1 beta secretion in response to cholesterol crystals in THP-1 cells and in human-monocytederived macrophages. HDL is able to blunt inflammatory monocyte cell recruitment in vivo following intraperitoneal CC injection in mice. HDL appears to modulate inflammasome activation in several ways. It reduces the loss of lysosomal membrane integrity following the phagocytosis of CC, but the major mechanism for the suppression of inflammasome activation by HDL is decreased expression of pro-IL-1 beta and NLRP3, and reducing caspase-1 activation. In summary, we have described a novel anti-inflammatory effect of HDL, namely its ability to suppress inflammasome activation by CC by modulating the expression of several key components of the inflammasome.

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