Heme oxygenase and indoleamine regulation by cytokines in cervical cancer cells and natural killer cells cytotoxic activity

Abstract

Objective: To determine the effect of the cytokines interleukin (IL-4), IL-10, Interferon gamma (IFN-γ) and tumor necrosis factor (TNF-α) in protein expression of HO-1 and IDO in cervical cancer cell lines and the cytotoxicity of NK cells in co-culture with cervix cancer cells pretreated with HO-1 and IDO inhibitors. Methods: The cervical cancer cell lines HeLa (HPV 18+), SiHa (HPV 16+) and C-33A (HPV -) were treated with 20 ng/mL of IL-4, IL-10, IFN-γ and TNF-α for 3 h, 6 h and 12 h, after that protein expression was assessed by flow cytometry. The cytotoxic activity of NK cells was performed in real time for 4 h. Results: Protein expression of the enzymes were changed at early times, increasing the expression of the enzymes in the 3 cell lines. We observed an increase in cytotoxic activity of NK cells cocultured with HeLa cells pretreated with the HO-1 inhibitor and in SiHa cells pretreated with the IDO inhibitor. Conclusion: The suppressor enzyme IDO is positively regulated by IL-10 in HeLa, SiHa, and NK cytotoxic activity increase in Hela and SiHa cells pretreated with HO-1 and IDO inhibitors respectively, which could be part of tumor escape mechanisms in cervix cancer.