title: Cervical cancer cell supernatants induce a phenotypic switch from U937-derived macrophage-activated M1 state into M2-like suppressor phenotype with change in Toll-like receptor profile.
abstract: Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages.
  
  
  RESULTS
  The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells.
  
  
  CONCLUSIONS
  Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages.
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, JAL, Mexico ; Programa de Doctorado en Ciencias Biomédicas Orientación Inmunología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, 44340 Guadalajara, JAL, 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, JAL, Mexico ; Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, 47600 Guadalajara, JAL, 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, JAL, 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, JAL, Mexico ; Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, 47600 Guadalajara, JAL, 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, JAL, 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, JAL, Mexico ; Programa de Doctorado en Ciencias Biomédicas Orientación Inmunología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, 44340 Guadalajara, JAL, 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, JAL, Mexico.
authors.forename: Ruth
authors.initials: R
authors.lastname: de Celis
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, JAL, 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, JAL, Mexico ; Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingeniería, Universidad de Guadalajara, 44430 Guadalajara, JAL, 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, JAL, Mexico.
authors.forename: Pablo Cesar
authors.initials: PC
authors.lastname: Ortiz-Lazareno
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D009569:Nitric Oxide