The interleukin-21 (IL-21) protein was found to be expressed at an elevated level in clinical samples of colorectal cancer patients without or with a parasitic infection that were collected from Sudan in our previous study. The IL-21 gene in HT29 and HCT116 cells was then correlated to cell proliferation and cell migration, as well as the cellular mechanisms associated with gene expressions in our present study. Our results demonstrated that silencing the IL-21 gene in HCT116 cells increased the cytotoxic level and fibroblast growth factor-4 (FGF4) mRNA expression in the cancer cells. Moreover, specific gene silencing reduced the migration of cancer cells compared to non-silenced cancer cells. These events were not observed in IL-21-silenced HT29 cells. Neutralizing FGF4 in conditioned medium of IL-21-silenced HCT116 cells further increased the cytotoxic level and restored the migratory activity of HCT116 cells in the culture compared to silencing the IL-21 gene alone in the cancer cells. Our results indicate the importance of both silencing the IL-21 gene and co-expression of the FGF4 protein in HCT116 cells, which pave the way for the discovery of important factors to be used as biomarkers for the design of drugs or cost-effective supplements to effectively treat the patients having infectious disease and HCT116 cells of colorectal cancer simultaneously in the future.

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 Toxoplasma gondii 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.

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