Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells.
Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells.
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Interleukin-17 通过刺激癌细胞中的 COX-2/PGE2 通路间接促进 M2 巨噬细胞分化
DOI：
10.4143/crt.2014.46.3.297
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发表时间：
2014-07
影响因子：
4.6
通讯作者：
You Z
中科院分区：
文献类型：
--
作者：
Li Q;Liu L;Zhang Q;Liu S;Ge D;You Z
目的白细胞介素17（IL-17）是一种促炎细胞因子，在炎症、自身免疫和肿瘤中发挥重要作用。本研究的目的是确定IL-17是否通过上调癌细胞系中的环氧化酶-2（考克斯-2）表达来间接调节巨噬细胞分化。材料与方法用重组IL-17作用于人宫颈癌HeLa、人肺癌A549和小鼠前列腺癌Myc-CaP/CR细胞株，采用Western blot、酶联免疫吸附试验和实时定量聚合酶链反应（RT-PCR）检测细胞反应。结果IL-17可上调HeLa、A549和Myc- CaP/CR细胞株考克斯-2 mRNA和蛋白的表达。IL-17的作用是通过核因子-κB和ERK 1/2信号通路介导的，这些通路的抑制剂可抑制IL-17诱导的考克斯-2表达。从癌细胞获得的条件培养基含有前列腺素E2，其水平通过IL-17处理而增加。当用条件培养基处理时，特别是用IL-17诱导的条件培养基处理时，小鼠RAW 264.7巨噬细胞和人THP-1单核细胞表达的IL-10（M2巨噬细胞的标志物）水平高于诱导型一氧化氮合酶或肿瘤坏死因子α（M1巨噬细胞的标志物）。相反，当RAW264.7和THP-1细胞直接用IL-17处理时，这些标记基因的表达没有显著改变。结论IL-17通过激活肿瘤细胞内的考克斯-2/PGE 2通路，间接促进M2巨噬细胞分化，从而间接调节肿瘤免疫微环境。
Purpose Interleukin-17 (IL-17) is a proinflammatory cytokine that plays important roles in inflammation, autoimmunity, and cancer. The purpose of this study was to determine if IL-17 indirectly regulates macrophage differentiation through up-regulation of cyclooxygenase-2 (COX-2) expression in the cancer cell lines. Materials and Methods Human cervical cancer HeLa, human lung cancer A549, and mouse prostate cancer Myc-CaP/CR cell lines were treated with recombinant IL-17; Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction analysis were utilized to examine the cellular responses. Results IL-17 up-regulated expression of COX-2 mRNA and protein in HeLa, A549, and Myc- CaP/CR cell lines. IL-17’s effects were mediated through nuclear factor-κB and ERK1/2 signaling pathways as the inhibitors of these pathways could inhibit IL-17- induced COX-2 expression. The conditional medium obtained from the cancer cells contained prostaglandin E2, the levels of which were increased by IL-17 treatment. When treated with the conditional medium, particularly with the IL-17-induced conditional medium, mouse RAW264.7 macrophages and human THP-1 monocytes expressed higher levels of IL-10 (a marker of M2 macrophages) than inducible nitric oxide synthase or tumor necrosis factor α (markers of M1 macrophages). In contrast, when RAW264.7 and THP-1 cells were treated directly with IL-17, expression of these marker genes was not markedly changed. Conclusion The results of this study suggest that IL-17 indirectly promotes M2 macrophage differentiation through stimulation of the COX-2/PGE2 pathway in the cancer cells, thus IL-17 plays an indirect role in regulating the tumor immune microenvironment.
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影响因子：
2.8
作者：
Steiner, GE;Newman, ME;Marberger, MJ
通讯作者：
Marberger, MJ
DOI：
10.4049/jimmunol.0902574
发表时间：
2010-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He D;Li H;Yusuf N;Elmets CA;Li J;Mountz JD;Xu H
通讯作者：
Xu H
DOI：
10.1152/ajpgi.00494.2001
发表时间：
2002-06-01
影响因子：
4.5
作者：
Hata, K;Andoh, A;Bamba, T
通讯作者：
Bamba, T
影响因子：
3.8
作者：
Ma J;Liu L;Che G;Yu N;Dai F;You Z
通讯作者：
You Z
可手术非小细胞肺癌不同pTNM分期CD4、IL17和Foxp3的表达及其对疾病预后的影响
影响因子：
--
作者：
Zhang, Guo-Qing;Han, Feng;Ma, Xiao-Mei
通讯作者：
Ma, Xiao-Mei