title: Interleukin-4 regulates macrophage polarization via the MAPK signaling pathway to protect against atherosclerosis.
abstract: Our study aimed to investigate the effects of interleukin-4 (IL-4) on macrophage polarization, as well as its role in the development of atherosclerosis. Human peripheral blood mononuclear cells (PBMCs) were isolated and randomly divided into 3 groups: control group, ox-LDL group, and ox-LDL + IL-4 groups. The expression of M1/M2 macrophage surface markers such as TNF-α, CD68, and CD206 were analyzed by western blot. Cell viability was determined using the MTT assay. Measurement of CD86/CD206 expression ratio (M1/M2 ratio) was performed via flow cytometry. In addition, ApoE(-/-) mice on a C57BL/6 background were subjected to high-fat diets, and were used as a model of atherosclerosis. Atherosclerotic lesion area was quantified after mice were treated with ox-LDL and IL-4. Finally, expression of phosphorylated MAPK signaling molecules such as p-ERK and p-JNK was quantified using western blot. The expression of TNF-α and CD86 markedly increased after cells were treated with ox-LDL, whereas the expression of CD206 markedly increased after PBMCs were treated with IL-4. It is possible that IL-4 could decrease ox-LDL-induced cell viability and the CD86/CD206 (M1/M2) ratio. Additionally, IL-4 intervention attenuated ox-LDL-induced atherosclerotic lesions in ApoE(-/-) mice, and decreased ox- LDL-induced expression of p-ERK and p-JNK. Our findings indicate that IL-4 may induce macrophages to take on an M2 phenotype in order to resolve inflammation via inhibition of MAPK signaling pathways, thereby protecting against atherosclerosis. IL-4 may serve as an intervention target for atherosclerosis.
authors.affiliation: Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: X N
authors.initials: XN
authors.lastname: Zhao
authors.affiliation: Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Y N
authors.initials: YN
authors.lastname: Li
authors.affiliation: Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Y T
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism*; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000494:pharmacology* / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D015847:Interleukin-4