Adiponectin Promotes Macrophage Polarization toward an Anti-inflammatory Phenotype
Adiponectin Promotes Macrophage Polarization toward an Anti-inflammatory Phenotype
复制标题
DOI：
10.1074/jbc.m109.088708
复制
发表时间：
2010-02-26
影响因子：
4.8
通讯作者：
Walsh, Kenneth
中科院分区：
文献类型：
--
作者：
Ohashi, Koji;Parker, Jennifer L.;Walsh, Kenneth
脂肪细胞衍生的细胞因子脂联素可以预防心血管和代谢性疾病，但这种脂肪因子对巨噬细胞极化（疾病进展的重要介质）的影响从未被评估过。我们假设脂联素调节巨噬细胞极化，从类似经典活化的M1表型到类似交替活化的m2细胞。从脂联素敲除小鼠中分离的腹腔巨噬细胞和脂肪组织的基质血管部分（SVF）细胞显示M1标记物增加，包括肿瘤坏死因子- α、白细胞介素-6和单核细胞趋化蛋白-1，M2标记物减少，包括精氨酸酶-1、巨噬细胞半乳糖n-乙酰半乳糖胺特异性凝集素-1和白细胞介素-10。在野生型和脂联素敲除小鼠的腹膜巨噬细胞和SVF细胞中，系统递送表达脂联素的腺病毒可显著增加精氨酸酶-1的表达。在培养中，重组脂联素蛋白处理巨噬细胞导致M2标记物水平升高，活性氧和活性氧相关基因表达减少。脂联素还能刺激人单核细胞来源的巨噬细胞和从人脂肪组织分离的SVF细胞中M2标记物的表达，并减弱M1标记物的表达。这些数据表明脂联素作为巨噬细胞极化的调节因子，它们表明高脂联素表达的条件可能通过促进巨噬细胞的抗炎表型来阻止代谢和心血管疾病的进展。
It is established that the adipocyte-derived cytokine adiponectin protects against cardiovascular and metabolic diseases, but the effect of this adipokine on macrophage polarization, an important mediator of disease progression, has never been assessed. We hypothesized that adiponectin modulates macrophage polarization from that resembling a classically activated M1 phenotype to that resembling alternatively-activated M2cells. Peritoneal macrophages and the stromal vascular fraction (SVF) cells of adipose tissue isolated from adiponectin knock-out mice displayed increased M1 markers, including tumor necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein-1 and decreased M2 markers, including arginase-1, macrophage galactose N-acetyl-galactosamine specific lectin-1, and interleukin-10. The systemic delivery of adenovirus expressing adiponectin significantly augmented arginase-1 expression in peritoneal macrophages and SVF cells in both wild-type and adiponectin knock-out mice. In culture, the treatment of macrophages with recombinant adiponectin protein led to an increase in the levels of M2 markers and a reduction of reactive oxygen species and reactive oxygen species-related gene expression. Adiponectin also stimulated the expression of M2 markers and attenuated the expression of M1 markers in human monocyte-derived macrophages and SVF cells isolated from human adipose tissue. These data show that adiponectin functions as a regulator of macrophage polarization, and they indicate that conditions of high adiponectin expression may deter metabolic and cardiovascular disease progression by favoring an anti-inflammatory phenotype in macrophages.