NF-κB pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment.

NF-κB pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment.
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NF-kappa B 通路参与肿瘤微环境中猪苓多糖对 RAW 264.7 巨噬细胞的 M1 极化

DOI:
10.1371/journal.pone.0188317
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Zeng X
Zeng X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu CP;Zhang X;Tan QL;Xu WX;Zhou CY;Luo M;Li X;Huang RY;Zeng X

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膀胱癌是与巨噬细胞密切相关的恶性肿瘤之一。多孔菌多糖(PPS)在治疗膀胱癌方面表现出良好的疗效,且副作用极小。然而,PPS抑制膀胱癌作用的分子机制尚不清楚。在这项研究中,我们使用单独培养的巨噬细胞或与T24人膀胱癌细胞培养上清液作为研究模型。我们发现PPS增强了IFN-γ刺激的RAW 264.7巨噬细胞的活性,表现为诱导型一氧化氮合酶(INOS)的释放、肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6的分泌、吞噬活性以及M1表型指标如CD 40、CD 284和CD 86的表达。PPS通过干扰IκB磷酸化,在核因子(NF)-κB信号通路的激活级联中起上游作用。此外,PPS还通过干扰Toll样受体(TLR)-4、INOS和环氧合酶(考克斯)-2调节NF-κB(P65)信号通路。我们的结果表明PPS通过TLR 4/NF-κB信号通路激活巨噬细胞。
Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86. PPS acted upstream in activation cascade of nuclear factor (NF)-κB signaling pathways by interfering with IκB phosphorylation. In addition, PPS regulated NF-κB (P65) signaling by interfering with Toll-like receptor (TLR)-4, INOS and cyclooxygenase (COX)-2. Our results indicate that PPS activates macrophages through TLR4/NF-κB signaling pathways.
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