重组IFN-α-2b-BCG对人PBMC的TLR4表达调节及其抗肿瘤作用的研究

TLR4 expression of human PBMC treated by recombinant IFN-α-2b-BCG and its anti-tumor effect

目的了解重组卡介苗(BCG)和野生BCG对人外周单核细胞(hPBMC)上TLR的调节差异,揭示hIFN-α-2b对hPBMC上TLR4的表达是否具有协同增强效应,以及BCG介导免疫细胞活化效应的新机制。方法比较研究重组hIFN-α-2b-BCG和野生型BCG,及其上清和等量干扰素对TLR4表达的调节,以及表达TLR4淋巴细胞的肿瘤杀伤效应。以淋巴细胞作为空白对照,应用流式细胞仪对TLR4进行检测,MTT法检测肿瘤细胞杀伤效应。结果证实了重组BCG和野生BCG对hPBMC的TLR4的表达均有正调节及抗肿瘤效应;重组BCG对hPBMC的TLR4表达的调节优于野生BCG(P<0.05);重组BCG上清和外源性等量干扰素对TLR4表达皆有正调节作用,但差别无统计学意义;重组BCG上清与野生BCG上清相比,对hPBMC诱导TLR4表达差别显著(P<0.05);与野生BCG组相比,重组BCG组表达TLR4的hPBMC杀伤肿瘤细胞的效应显著增强(P<0.05)。结论重组BCG的脂多糖和持续分泌的hIFN-α-2b对hPBMC的TLR4表达均有正调节作用,并加强表达TLR4淋巴细胞的细胞介导的抗肿瘤效应。

Objective To investigate TLR4 expression of human peripheral blood mononuclear cells（hPBMC）treated with recombinant hIFN-α-2b-BCG and its anti-tumor effect.Methods hPBMCs were treated with hIFN-α-2b-BCG（rBCG）or wild-type BCG（wBCG）in vitro.TLR4 expression of hPBMCs was detected by flow cytometry and anti-tumor effect was measured by MTT assay.Results The expression of TLR4 in hPBMCs treated with rBCG was stronger than that treated with BCGs（P〈0.05）.Both supernatant of rBCG-treated hPBMCs and equivalent exogenous interferon induced TLR4 expression,and the effects were not different.The expression of TLR4 induced by rBCG-treated supernatant was significantly higher than that treated by wBCG（P〈0.05）.The anti-tumor effect of hPBMC expressing TLR4 induced by rBCG significantly increased,compared with that of wBCG（P〈0.05）.Conclusion Recombinant hIFN-α-2b-BCG can enhance TLR4 expression of hPBMCs and its TLR4-mediated anti-tumor effect.