腫瘤組織中乳酸對DC活化和功能的影響
發(fā)布時間:2018-06-04 14:08
本文選題:樹突狀細胞 + 腫瘤微環(huán)境。 參考:《免疫學雜志》2017年05期
【摘要】:目的探討腫瘤微環(huán)境中的乳酸對樹突狀細胞(dendritic cells,DC)活化和功能的影響。方法取C57BL/6小鼠骨髓細胞誘導其分化為DC,并加入脂多糖(lipopolysaccharides,LPS)促進其活化;隨后采用腫瘤培養(yǎng)上清或乳酸作用于活化的DC,通過流式細胞術、ELISA、T細胞增殖實驗、Western blot等方法檢測DC細胞的活化程度,并對乳酸影響DC活化的信號通路進行分析。結果乏氧狀態(tài)的腫瘤細胞釋放更多的乳酸,乳酸可以抑制DC細胞共刺激因子CD80、CD86和MHCⅡ的表達,并下調(diào)TNF-α和IL-12的表達,從而抑制DC對T細胞活化增殖的促進作用;乳酸通過降低DC的NF-κB和p38MAPK信號通路的活化影響DC活化。結論腫瘤組織乏氧狀態(tài)釋放大量的乳酸,乳酸通過抑制DC細胞的活化進而影響抗腫瘤免疫反應的激活。
[Abstract]:Objective to investigate the effects of lactic acid in tumor microenvironment on the activation and function of dendritic cells (DC). Methods C57BL/6 mouse bone marrow cells were induced to differentiate into DCS and lipopolysaccharide LPSs were added to promote its activation. Then the activated DCs were treated with tumor culture supernatant or lactic acid, and the activation degree of DC cells was detected by flow cytometry (FCM) and EISAT cell proliferation assay (EISAT cell proliferation assay), and the signal pathway of lactic acid affecting DC activation was analyzed. Results the tumor cells in hypoxic state released more lactic acid, which could inhibit the expression of CD80, CD80, CD86 and MHC 鈪,
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