IL-34 promotes foam cell formation by enhancing CD36 expression through p38 MAPK pathway

Area of Science:

• Immunology
• Cardiovascular Biology
• Cell Biology

Background:

• Atherosclerosis is a chronic inflammatory disease driven by macrophage-derived foam cells.
• Interleukin-34 (IL-34) is implicated in inflammatory and autoimmune conditions, with elevated expression in diseases like rheumatoid arthritis and coronary artery disease.
• The specific role of IL-34 in atherosclerosis pathogenesis is currently unknown.

Purpose of the Study:

• To investigate the role of IL-34 in the development of macrophage foam cells.
• To elucidate the molecular mechanisms by which IL-34 influences lipid metabolism and inflammation in macrophages.
• To assess the potential of IL-34 as a biomarker for atherosclerosis.

Main Methods:

• Bone marrow-derived macrophages (BMDMs) were treated with IL-34 and oxidized low-density lipoprotein (oxLDL).
• Intracellular cholesterol content and cholesterol efflux were measured.
• CD36 expression and pro-inflammatory cytokine levels were analyzed.
• The p38 MAPK signaling pathway was investigated.

Main Results:

• IL-34 treatment significantly increased oxLDL uptake and intracellular cholesterol accumulation in BMDMs.
• IL-34 promoted foam cell formation by up-regulating CD36 expression via the p38 MAPK pathway.
• IL-34 enhanced oxLDL-induced pro-inflammatory cytokine production.
• IL-34 did not affect cholesterol efflux.

Conclusions:

• IL-34 facilitates foam cell formation in macrophages by enhancing CD36-mediated lipid uptake.
• IL-34 promotes inflammation associated with atherosclerosis.
• IL-34 represents a potential novel risk biomarker for atherosclerosis.