Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype.
Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype.
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Protectin DX 通过改善炎症和调节巨噬细胞表型来提高脓毒症小鼠模型的存活率
DOI：
10.1038/s41598-017-00103-0
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发表时间：
2017-03-07
影响因子：
4.6
通讯作者：
Yao S
中科院分区：
文献类型：
--
作者：
Xia H;Chen L;Liu H;Sun Z;Yang W;Yang Y;Cui S;Li S;Wang Y;Song L;Abdelgawad AF;Shang Y;Yao S
最近，一系列研究表明，源自欧米茄3的脂肪介导子，在许多炎症性疾病中，脂肪酸docosahecahecahecaenoic Acid具有促疾病的脂肪酸或抗炎作用。是通过盲肠结扎建立的穿刺（CLP）。 ERS（arg1和ym1）及其转录调节剂（过氧化物体激活的受体-γ，PPAR-γ）被PDX挑战的RAW264.7巨噬细胞上调。巨噬细胞的促进活性和加速炎症的分辨率，最终导致化粪池小鼠的存活率提高。
Recently, a serial of studies have demonstrated that lipid mediators derived from Omega-3 fatty acid docosahexaenoic acid have pro-resolving or anti-inflammatory effects in many inflammatory diseases. Here, we sought to evaluate whether Protectin DX (PDX, an isomer of Protecin D1), a newly identified lipid mediator, could protect mice against sepsis and explore the underling mechanism. Animal model of sepsis was established by cecum ligation and puncture (CLP). We found that PDX increased overall survival rate within eight days and attenuated multiple organ injury in septic mice. In addition, PDX reduced pro-inflammatory cytokines and bacterial load 24 h after CLP. Moreover, PDX promoted phagocytosis of peritoneal macrophages and increased the percentage of M2 macrophages in peritoneum of septic mice.In vitro, M2 macrophage markers (Arg1 and Ym1) and its transcriptional regulator (peroxisome proliferator-activated receptor-γ, PPAR-γ) were upregulated in Raw264.7 macrophages challenged with PDX. GW9662 (a PPAR-γ inhibitor) and PPAR-γ siRNA abrogated the induction of Arg1 and Ym1 by PDX in Raw264.7 cells. Taken together, our results suggest that PDX is able to promote M2 polarization, enhance phagocytosis activity of macrophage and accelerate resolution of inflammation, finally leading to increased survival rate of septic mice.