Ge Peng, Ong Ching Yi, Abdalkareem Abdalla Eshtiyag, Khoo Boon Yin, Yuan Bo
Department of General Surgery, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China.
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, Malaysia.
Exp Ther Med. 2021 Feb;21(2):103. doi: 10.3892/etm.2020.9535. Epub 2020 Nov 27.
The presence of certain soluble factors may provide a possible selective advantage for a parasite to gradually modify cell proliferation in neighbouring cells, which may result in chronic diseases. These soluble factors present in the conditioned medium also allow the parasite to invade rapidly into more host cells. The present study aimed to determine the levels of a group of type 1 T helper (Th1) cytokines in the conditioned media of host cells infected with parasites and in IL-21-silenced colorectal cancer cells. The conditioned media of human foreskin fibroblasts (HFFs) parasitized with the RH and ME49 strains of for 10 days were prepared, and subsequently the levels of the Th1 cytokines in the conditioned media were determined by ELISA. HFFs were incubated with the growth media containing selected soluble factors, and cell proliferation markers were subsequently analysed by reverse transcription-quantitative PCR. The mRNA expression level of cell proliferation markers was also examined in IL-21-silenced HCT116 cells, where the levels of soluble factors in the conditioned media were also determined as aforementioned. The results of the present study demonstrated that HFFs parasitized with ME49 released elevated levels of IFN-γ and lower levels of IL-18 into the conditioned medium compared with the controls. These phenomena were not observed in the conditioned medium of HFFs parasitized with RH. Similar levels of these soluble factors were also detected in the conditioned medium of IL-21-silenced HCT116 cells. The results of the present study also revealed that Ki67 and proliferating cell nuclear antigen mRNA expression was altered in host cells incubated with various levels of IFN-γ and IL-18, as well as in IL-21-silenced HCT116 cells compared with the respective controls. In conclusion, the current study provided preliminary evidence on the fundamental molecular mechanisms of host-parasite interactions that result in chronic diseases, which may aid in the treatment of these diseases in the relevant endemic regions.
某些可溶性因子的存在可能为寄生虫逐步改变邻近细胞的增殖提供一种潜在的选择优势，这可能导致慢性疾病。条件培养基中存在的这些可溶性因子还使寄生虫能够迅速侵入更多宿主细胞。本研究旨在测定感染寄生虫的宿主细胞条件培养基以及白细胞介素-21（IL-21）沉默的结肠癌细胞中一组1型辅助性T细胞（Th1）细胞因子的水平。制备了用人包皮成纤维细胞（HFFs）分别感染RH和ME49株寄生虫10天的条件培养基，随后通过酶联免疫吸附测定（ELISA）法测定条件培养基中Th1细胞因子的水平。将HFFs与含有选定可溶性因子的生长培养基一起孵育，随后通过逆转录定量聚合酶链反应（RT-qPCR）分析细胞增殖标志物。还检测了IL-21沉默的HCT116细胞中细胞增殖标志物的信使核糖核酸（mRNA）表达水平，其中条件培养基中的可溶性因子水平也如上述测定。本研究结果表明，与对照组相比，感染ME49的HFFs向条件培养基中释放的γ-干扰素（IFN-γ）水平升高，白细胞介素-18（IL-18）水平降低。在感染RH的HFFs的条件培养基中未观察到这些现象。在IL-21沉默的HCT116细胞的条件培养基中也检测到了这些可溶性因子的类似水平。本研究结果还显示，与各自的对照组相比，在用不同水平的IFN-γ和IL-18孵育的宿主细胞以及IL-21沉默的HCT116细胞中，Ki67和增殖细胞核抗原mRNA表达发生了改变。总之，本研究为导致慢性疾病的宿主-寄生虫相互作用的基本分子机制提供了初步证据，这可能有助于在相关流行地区治疗这些疾病。
