Abstract
Atherosclerosis is characterized as a chronic inflammatory disease and macrophage-derived foam cells play a central role during the pathologic processes. A newly discovered cytokine interleukin-34 (IL-34) is closely associated with various inflammatory and autoimmune diseases. Expression of IL-34 in obesity, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), lupus nephritis and coronary artery diseases (CAD) are significantly elevated. However, the role of IL-34 in atherosclerosis remains unknown. In our present study, we found that IL-34 treatment markedly increased the uptake of oxLDL, intracellular total and esterified cholesterol content but not cholesterol efflux, subsequently promoted foam cell formation through up-regulating CD36 expression via p38 MAPK signal pathway in bone marrow derived macrophages (BMDMs). Furthermore, treatment with IL-34 significantly elevated the oxLDL-induced up-regulation of pro-inflammatory cytokines. Our results conclude that IL-34 facilitates foam cell formation by increasing CD36-mediated lipid uptake and suggest a potential new risk biomarker for atherosclerosis.
Highlights
Cardiovascular diseases still remain to be the leading cause of mortality and morbidity worldwide[1,2]
Atherosclerosis has been considered as a chronic inflammatory disease characterized by the recruitment of immunocytes, and a devil of inflammatory cytokines involved in macrophage lipid metabolism[13]
We investigated whether IL-34 plays a role in macrophage cholesterol efflux. 3H-labeled cholesterol tracer was used to analyze the efflux to lipid-poor ApoA-I or HDL
Summary
Cardiovascular diseases still remain to be the leading cause of mortality and morbidity worldwide[1,2]. Macrophages activated with IL-34 in vitro had an augmented capacity of oxLDL uptake by an enhancement of mRNA and protein expression of CD36 as well as aggravated secretion of pro-inflammatory cytokines and resulted in promoting foam cell formation. Results IL-34 enhanced macrophage cholesterol accumulation and promoted foam cell formation.
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