TY - JOUR
T1 - Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13
AU - Gao, Shanshan
AU - Zhou, Juan
AU - Liu, Na
AU - Wang, Lijun
AU - Gao, Qiyue
AU - Wu, Yan
AU - Zhao, Qiang
AU - Liu, Peining
AU - Wang, Shun
AU - Liu, Yan
AU - Guo, Ning
AU - Shen, Yan
AU - Wu, Yue
AU - Yuan, Zuyi
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Aims: To address the underlying mechanisms by which curcumin facilitates M2 phenotype polarization of macrophages and its roles in the protective effects during experimental autoimmune myocarditis (EAM). Methods and results: The expression of classic M2 markers, including macrophage mannose receptor (MMR), arginase-1 (Arg-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) was upregulated in curcumin-treated Raw264.7 macrophages. Curcumin increased interleukin-4 (IL-4) and interleukin-13 (IL-13) mRNA expression and protein secretion. Curcumin notably increased STAT6 phosphorylation. Leflunomide, a STAT6 inhibitor, and IL-4 and/or IL-13 neutralizing antibodies antagonized the induction of MMR, Arg-1 and PPAR-γ by curcumin in Raw264.7 cells. In vivo, 6-week old male Lewis rats were used to induce EAM and orally administrated with curcumin or corn oil for 3weeks after myosin injection. Cardiac functional parameters, including left ventricular fractional shortening (LVFS), ejection fraction (EF), left ventricular end-systolic diameter (LVEDs) and heart rate (HR) were significantly improved by curcumin treatment. Curcumin also reduced the inflammatory cell infiltration and myocardial mRNA levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Meanwhile, the myocardial mRNA levels of MMR and Arg-1 were markedly up-regulated by curcumin. Immunofluorescence assay showed that the number of CD68+ MMR+ and CD68+ Arg-1+ double positive macrophages in curcumin-treated myocardial tissue was significantly higher than untreated control. The number of CD68+ iNOS+ double positive macrophages was increased obviously in EAM group, but decreased markedly by curcumin treatment. Conclusions: Taken together, these results show that curcumin induces macrophage M2 polarization by secretion of IL-4 and/or IL-13. Curcumin ameliorates EAM by reducing infiltration inflammatory macrophages and by polarizing M0 and M1 macrophages to M2 phenotype.
AB - Aims: To address the underlying mechanisms by which curcumin facilitates M2 phenotype polarization of macrophages and its roles in the protective effects during experimental autoimmune myocarditis (EAM). Methods and results: The expression of classic M2 markers, including macrophage mannose receptor (MMR), arginase-1 (Arg-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) was upregulated in curcumin-treated Raw264.7 macrophages. Curcumin increased interleukin-4 (IL-4) and interleukin-13 (IL-13) mRNA expression and protein secretion. Curcumin notably increased STAT6 phosphorylation. Leflunomide, a STAT6 inhibitor, and IL-4 and/or IL-13 neutralizing antibodies antagonized the induction of MMR, Arg-1 and PPAR-γ by curcumin in Raw264.7 cells. In vivo, 6-week old male Lewis rats were used to induce EAM and orally administrated with curcumin or corn oil for 3weeks after myosin injection. Cardiac functional parameters, including left ventricular fractional shortening (LVFS), ejection fraction (EF), left ventricular end-systolic diameter (LVEDs) and heart rate (HR) were significantly improved by curcumin treatment. Curcumin also reduced the inflammatory cell infiltration and myocardial mRNA levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Meanwhile, the myocardial mRNA levels of MMR and Arg-1 were markedly up-regulated by curcumin. Immunofluorescence assay showed that the number of CD68+ MMR+ and CD68+ Arg-1+ double positive macrophages in curcumin-treated myocardial tissue was significantly higher than untreated control. The number of CD68+ iNOS+ double positive macrophages was increased obviously in EAM group, but decreased markedly by curcumin treatment. Conclusions: Taken together, these results show that curcumin induces macrophage M2 polarization by secretion of IL-4 and/or IL-13. Curcumin ameliorates EAM by reducing infiltration inflammatory macrophages and by polarizing M0 and M1 macrophages to M2 phenotype.
KW - Curcumin
KW - Experimental autoimmune myocarditis
KW - M2 macrophages
UR - https://www.scopus.com/pages/publications/84930634376
U2 - 10.1016/j.yjmcc.2015.04.025
DO - 10.1016/j.yjmcc.2015.04.025
M3 - 文章
C2 - 25944087
AN - SCOPUS:84930634376
SN - 0022-2828
VL - 85
SP - 131
EP - 139
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -