趋化因子
四氯化碳
巨噬细胞极化
基因敲除
M2巨噬细胞
细胞生物学
MAPK/ERK通路
p38丝裂原活化蛋白激酶
趋化性
癌症研究
化学
炎症
信号转导
医学
巨噬细胞
免疫学
生物
内科学
细胞凋亡
体外
生物化学
受体
作者
Liang-Wei Chen,Dihao Pan,Yiran Zhang,Enfan Zhang,Liang Ma
出处
期刊:Journal of Interferon and Cytokine Research
[Mary Ann Liebert]
日期:2024-02-01
卷期号:44 (2): 68-79
标识
DOI:10.1089/jir.2023.0132
摘要
Macrophages are crucial immune cells that play essential roles in the healing of myocardial infarction (MI), undergoing continuous polarization throughout this process. C-C motif chemokine 2 (CCL2) is a chemokine that regulates inflammatory responses during MI. However, the extent to which CCL2 influences macrophage polarization and MI healing remains incompletely understood. In this study, we investigate the role of CCL2 in macrophage polarization and MI healing. Our findings reveal that CCL2 is differentially expressed in lipopolysaccharide (LPS)-induced M1 and interleukin (IL)-4-induced M2 RAW264.7 macrophages. Knockdown of CCL2 attenuates TNF-α secretion stimulated by LPS, while overexpression of CCL2 mitigates IL-10 production triggered by IL-4 in these macrophages. Moreover, CCL2 deficiency disrupts LPS-induced M1 polarization, whereas CCL2 overexpression reduces M2 polarization of RAW264.7 macrophages induced by IL-4. Further exploration indicates that the promotion of M1 polarization by CCL2 is significantly impaired by inhibition of the p38-mediated MAPK pathway and NF-κB pathway. In a MI mouse model, CCL2 knockdown remarkably reduces infarct size, collagen synthesis, and the expression of cardiac fibrosis and hypertrophy markers. The activity of the p38-mediated MAPK pathway and NF-κB pathway is downregulated by CCL2 knockdown as well. Additionally, the number of total macrophages and M1 macrophages in the infarct decreases, while the number of M2 macrophages increases upon CCL2 deficiency. In conclusion, these results suggest that CCL2 is a key regulator of macrophage polarization, controlling MI healing in vivo.
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