OxLDL-induced IL-1 beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation

Inflamm Res. 2014 Jan;63(1):33-43. doi: 10.1007/s00011-013-0667-3.


Objective: IL-1β is a master switch of inflammation and plays an important role in the pathogenesis of vascular disease. During early atherosclerosis development, it is not clearly understood how oxidized low density lipoprotein (oxLDL)induced signaling pathways control NLRP3 inflammasome activation and produce IL-1β and promote foam cells formation.

Methods: The study used THP-1 macrophage as cell model. Western blot quantified the oxLDL-induced NLRP3 inflammasome related proteins. The FACS detected the expression of SR-A and CD36 receptors on the cells, and caspase-1 activation in the cells. The DCFH-DA assayed the reactive oxygen species (ROS). Oil red O staining techniques examined the intracellular lipid droplet.

Results: The OxLDL remarkably increased not only IL-1β mRNA transcription and pro-IL-1β protein synthesis but also IL-1β secretion in human macrophages. The activation of the NLRP3 inflammasome depended on oxLDL-induced generation of ROS, potassium efflux and cathepsin B activity. The OxLDL-induced ROS production that mediates IL-1β maturation mainly depended on the scavenger receptor of CD36 but not SR-A. The secreted IL-1β served as an autocrine function for promoting macrophage foam cells formation.

Conclusions: These findings suggest that oxLDL-induced NLRP3 inflammasome activation mainly depends on CD36 involved in the progression of atherosclerosis by promoting oxLDL-mediated inflammation and foam cell formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD36 Antigens / genetics*
  • Carrier Proteins / genetics*
  • Caspase 1 / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Foam Cells / cytology*
  • Humans
  • Inflammasomes / genetics*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Leukocytes, Mononuclear / cytology
  • Lipoproteins, LDL / pharmacology*
  • Macrophages / cytology
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Reactive Oxygen Species / metabolism
  • Scavenger Receptors, Class A / genetics


  • CD36 Antigens
  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Lipoproteins, LDL
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Scavenger Receptors, Class A
  • oxidized low density lipoprotein
  • Caspase 1