Heme oxygenase and indoleamine regulation by cytokines in cervical cancer cells and natural killer cells cytotoxic activity
Pablo C. Ortiz-Lazareno 1, Paulina Gómez-Lomeli 2, Georgina Hernández-Flores 3, Cristina Rodríguez-Padilla 4, Francisco Javier Ochoa-Carrillo 5, Alejandro Bravo-Cuellar 6
1 División de Inmunología, Centro de Investigación Biomédica de Occidente, IMSS IMSS, Guadalajara, Jal., México; 2 División de Inmunología, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Jal., México; 3 División de Inmunología, Centro de Investigación Biomédica de Occidente, IMSS IMSS, Guadalajara, Jalisco, México; 4 Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., México; 5 Editor in Chief, Gaceta Mexicana de Oncología (GAMO), Mexico City, Mexico; 6 División de Inmunología, Centro de Investigación Biomédica de Occidente, IMSS IMSS, Guadalajara; Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos; Jal., México
Pablo C. Ortiz-Lazareno, Paulina Gómez-Lomeli, Georgina Hernández-Flores, Cristina Rodríguez-Padilla, Francisco Javier Ochoa-Carrillo, Alejandro Bravo-Cuellar
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*Correspondencia: Alejandro Bravo-Cuellar, Email no disponible
Resumen
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.
