title: Increase of IFN-γ and TNF-α production in CD107a + NK-92 cells co-cultured with cervical cancer cell lines pre-treated with the HO-1 inhibitor.
abstract: BACKGROUND
  Natural killer (NK) cells eliminate virus-infected and tumor cells through the release of perforins and granzymes; they also produce Interferon gamma (IFN-γ) and Tumor necrosis factor alpha (TNF-α), which induce apoptosis in target cells. Many tumors express Heme oxygenase 1 (HO-1), and this expression has been associated with avoiding immunosuppression and apoptosis. In this work, HO-1+ Cervical cancer cell (CCC) lines were pre-treated with HO-1 inhibitor and we assessed whether this inhibition enhanced the sensitivity of CCC to NK cell activity.
  
  
  METHODS
  We assessed the expression of HO-1 in HeLa, SiHa, and C-33A CCC by Flow cytometry (FC). CCC were pre-treated with SnPP or ZnPP HO-1 inhibitors. After that, NK-92 cells were co-cultured with HeLa, SiHa, and C-33A CCC pre-treated or not with HO-1 inhibitors, and the expression of IFN-γ, TNF-α, CD107a, Granzyme B, NKp44, NKp46, NKp30, and NKG2D was evaluated by FC.
  
  
  RESULTS
  CCC lines HeLa, SiHa, and C-33A expressed HO-1. Inhibition of HO-1 in these cells increased the expression of IFN-γ and TNF-α in CD107a + NK-92 cells. We observed a reduction in the expression of NKG2D, NKp46, and NKp30 in NK cells co-cultured with HeLa and SiHa cells, and when HeLa and SiHa cells were pre-treated with the HO-1 inhibitors, the expression of NKG2D and NKp30 in NK cells was restored. We observed a similar effect in NK cells co-cultured with C-33A cells in NKp30 expression.
  
  
  CONCLUSIONS
  Inhibition of HO-1 in CCC induces an increase in IFN-γ and TNF-α production in CD107a + NK-92 cells and restores NKG2D, NKp46 and NKp30 downmodulation in NK cells.
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico ; Programa de Doctorado en Ciencias Biomédicas Orientación Inmunología, Centro Universitario de Ciencias de la Salud (CUCS), UdeG, Guadalajara, Jalisco Mexico.
authors.forename: Paulina
authors.initials: P
authors.lastname: Gómez-Lomelí
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico ; Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara (UdeG), Tepatitlán de Morelos, Jalisco Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bravo-Cuellar
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico.
authors.forename: Georgina
authors.initials: G
authors.lastname: Hernández-Flores
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico.
authors.forename: Luis Felipe
authors.initials: LF
authors.lastname: Jave-Suárez
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguilar-Lemarroy
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico ; Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara (UdeG), Tepatitlán de Morelos, Jalisco Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lerma-Díaz
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico ; Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingeniería, UdeG, Guadalajara, Jalisco Mexico.
authors.forename: Jorge Ramiro
authors.initials: JR
authors.lastname: Domínguez-Rodríguez
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico ; Programa de Doctorado en Ciencias Biomédicas Orientación Inmunología, Centro Universitario de Ciencias de la Salud (CUCS), UdeG, Guadalajara, Jalisco Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Sánchez-Reyes
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico.
authors.forename: Pablo Cesar
authors.initials: PC
authors.lastname: Ortiz-Lazareno
keywords: Cervical cancer cells; Heme oxygenase 1; IFN-γ; NK cells; NKG2D; NKp30; TNF-α