Analysis of the contribution of nasopharyngeal epithelial cancer cells to the induction of a local inflammatory response

Analysis of the contribution of nasopharyngeal epithelial cancer cells to the induction of a local inflammatory response
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鼻咽上皮癌细胞对诱导局部炎症反应的贡献分析

DOI:
10.1007/s00432-011-1066-1
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发表时间:
2012-01-01
影响因子:
3.6
通讯作者:
Li, Guiyuan
Li, Guiyuan
中科院分区:
医学3区
文献类型:
--
作者:
Liao, Qianjin;Guo, Xiaofang;Li, Guiyuan

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PurposeWe investigated the local contribution of nasopharyngeal epithelial cancer cells to inflammatory process.Materials and methodsTHP-1 monocytes用佛波醇12-肉豆蔻酸酯13-乙酸酯处理诱导分化的巨噬细胞(D-THP-1)的产生,随后用脂多糖(LPS)(10 ng/ml)激活。ELISA和qRT-PCR检测D-THP-1细胞中促炎细胞因子的产生。从细胞增殖(MTT)、促炎细胞因子产生(ELISA)以及NF-κB和STAT 3活化方面研究从LPS处理的D-THP-1细胞收获的条件培养基的作用结果LPS诱导鼻咽癌细胞株5- 8 F产生促炎细胞因子TNF-α IL-6(42.2 ± 5.32 pg/ml)、IL-1β(9.6 ± 1.34 pg/ml)和IL-8(19.3 ± 3.47 pg/ml)在D-THP-1细胞中的表达水平与mRNA水平的表达水平相似,差异有显著性(P< 0.001)。LPS处理的D-THP-1细胞条件培养液可显著诱导5- 8 F细胞产生TNF-α(632.3 ± 71.32 pg/ml),IL-6(51.3 ± 3.57 pg/ml),IL-1β(7.3 ± 1.31 pg/ml)和IL-8(20.1 ± 2.36 pg/ml)(P< 0.01)并触发NF-κB和STAT 3的显著活化,与IκBα的降解和JAK 2磷酸化的增加相关(P< 0.05)。LPS处理的D-THP-1条件培养基能促进5- 8 F细胞的增殖结论鼻咽上皮癌细胞可能通过激活NF-κB和STAT 3通路,局部产生促炎细胞因子,在维持和放大炎症过程中发挥重要作用。其在鼻咽通路中募集和激活额外的免疫细胞并促进肿瘤进展。
PurposeWe investigated the local contribution of nasopharyngeal epithelial cancer cells to the inflammatory process.Materials and methodsTHP-1 monocytes were treated with phorbol 12-myristate 13-acetate to induce the production of differentiated macrophages (D-THP-1), which were subsequently activated by lipopolysaccharide (LPS) (10 ng/ml). The production of pro-inflammatory cytokines in D-THP-1 cells was detected by ELISA and qRT-PCR. The effects of conditioned media harvested from LPS-treated D-THP-1 cells were investigated with regard to cell proliferation (MTT), production of pro-inflammatory cytokines (ELISA) and activation of NF-κB and STAT3 (western blot) in the nasopharyngeal epithelial cancer cell line 5–8F.ResultsLPS induced the production of the pro-inflammatory cytokines TNF-α (875.1 ± 68.31 pg/ml), IL-6 (42.2 ± 5.32 pg/ml), IL-1β (9.6 ± 1.34 pg/ml) and IL-8 (19.3 ± 3.47 pg/ml) in D-THP-1 cells significantly (P< 0.001) with similar results detected at the mRNA level. Exposure of 5–8F cells to conditioned medium from LPS-treated D-THP-1 cells significantly induced production of TNF-α (632.3 ± 71.32 pg/ml), IL-6 (51.3 ± 3.57 pg/ml), IL-1β (7.3 ± 1.31 pg/ml) and IL-8 (20.1 ± 2.36 pg/ml) (P< 0.01) and triggered significant activation of NF-κB and STAT3, which correlated with a concomitant degradation of IκBα and an increase in JAK2 phosphorylation (P< 0.05). Moreover, the LPS-treated D-THP-1 conditioned media promoted the proliferation of 5–8F cells (P< 0.05).ConclusionsNasopharyngeal epithelial cancer cells may play a significant role in maintaining and amplifying the inflammation process via activation of NF-κB and STAT3 pathway and through the local production of pro-inflammatory cytokines, which recruit and activate additional immune cells in the nasopharyngeal path and promote tumour progression.