Molecular analysis of curcumin-induced polarization of murine RAW264.7 macrophages.
This study aimed to investigate the effects of curcumin on macrophages polarization and possible mechanism involved, and to analyze the molecular basis of its antiatherosclerosis activity. RAW264.7 macrophages (M0) and M1 macrophages were treated with curcumin at 0, 6.25, 12.5, and 25 μmol/L with or without GW9662. Using real-time polymerase chain reaction and Western blot analysis, we examined the phenotype markers of M1 [iNOS, interleukin (IL)-1β, IL-6, and MCP-1] and M2 (KLF4, FIZZ1, and MGL1] macrophages. Curcumin reduced the expression of the M1 phenotype markers and upregulated the expression of proliferator-activated receptor γ in M0 and M1 macrophages and IKBα in M1 macrophages. When M1 macrophages were incubated with curcumin and GW9662, the expression of the M1 phenotype markers was decreased, while IKBα was upregulated. The expression of the M2 phenotype markers in M0 and M1 macrophages was upregulated after the curcumin treatment. When M0 and M1 macrophages were incubated with curcumin and GW9662, the expression of the M2 phenotype markers was reduced. Curcumin inhibited the M1 inflammation phenotype as a result of the direct activation of IKBα and polarized the macrophages to become M2 phenotype through the activation of proliferator-activated receptor γ. These findings provide new clues to develop new drug therapy for atherosclerosis.
*Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China; †Department of Forensic Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, China; and ‡Department of Cardiovascular Medicine, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
Fangyuan
F
Chen
Ning
N
Guo
Guofen
G
Cao
Juan
J
Zhou
Zuyi
Z
Yuan
D000818:Animals; D016764:Cell Polarity / Q000187:drug effects* / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000090062:Kruppel-Like Factor 4; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice
C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D003474:Curcumin