R Solís-Martínez1, M Cancino-Marentes2, G Hernández-Flores3, P Ortiz-Lazareno3, G Mandujano-Álvarez4, C Cruz-Gálvez2, E Sierra-Díaz5, C Rodríguez-Padilla6, L F Jave-Suárez3, A Aguilar-Lemarroy3, A Bravo-Cuellar7. 1. Programa de Doctorado en Ciencias Biomédicas Orientación Inmunología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, CP 44340 Guadalajara, Jal., Mexico. 2. Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, CP 44340 Guadalajara, Jal., Mexico. 3. División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, CP 44340 Guadalajara, Jal., Mexico. 4. Hospital Médica Tabasco, DACS, UJAT, Av. Paseo Tabasco 808, CP 86040 Villahermosa, Tabasco, México. 5. Servicio de Urología, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), CP 44340 Guadalajara, Jal., Mexico. 6. Departamento de Virología e Inmunología, Universidad Autónoma de Nuevo León. Av. Pedro de Alba S/N, Ciudad Universitaria, Apartado Postal 46-F, CP 66450 San Nicolás de los Garza, Nuevo León, Mexico. 7. División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, CP 44340 Guadalajara, Jal., Mexico; Centro Universitario de los Altos (CUALTOS), Universidad de Guadalajara, CP 47600 Tepatitlán de Morelos, Jal., Mexico. Electronic address: abravoc@prodigy.net.mx.
Abstract
BACKGROUND: Transcription factor STAT3 has a prominent innate immunity effect on cancer progression. We determined the regulation of STAT3 in the immunophenotype modulation of macrophages from M1 into M2 induced by the cell-culture supernatant of the Prostate-Cancer line PC3. METHODS: Monocytes-macrophages from healthy donors were cultured in the supernatant of PC3 cells, membrane proteins, and intracytoplasmic and phosphorylated STAT3 were measured using flow cytometry, while cytokines and growth factors were studied using luminescence. Cytotoxicity and nitric oxide were evaluated via colorimetric assays. RESULTS: The supernatant of PC3 prostate-tumor cells effectively induced macrophages toward an M2 profile, and the expression of phosphorylated STAT3 in the monocytes-macrophages notably increased, and mainly related to IL-10. In the group of monocytes-macrophages treated with a STAT3 inhibitor, the macrophages were induced toward an M1 phenotype. CONCLUSIONS: In this study, we showed that the secretion profile of PC3 prostate-cancer cells induces a change in macrophage phenotype from M1 into M2, and that the phenomenon is related to phosphorylation of transcription factor STAT3 and IL-10.
BACKGROUND: Transcription factor STAT3 has a prominent innate immunity effect on cancer progression. We determined the regulation of STAT3 in the immunophenotype modulation of macrophages from M1 into M2 induced by the cell-culture supernatant of the Prostate-Cancer line PC3. METHODS: Monocytes-macrophages from healthy donors were cultured in the supernatant of PC3 cells, membrane proteins, and intracytoplasmic and phosphorylated STAT3 were measured using flow cytometry, while cytokines and growth factors were studied using luminescence. Cytotoxicity and nitric oxide were evaluated via colorimetric assays. RESULTS: The supernatant of PC3 prostate-tumor cells effectively induced macrophages toward an M2 profile, and the expression of phosphorylated STAT3 in the monocytes-macrophages notably increased, and mainly related to IL-10. In the group of monocytes-macrophages treated with a STAT3 inhibitor, the macrophages were induced toward an M1 phenotype. CONCLUSIONS: In this study, we showed that the secretion profile of PC3prostate-cancer cells induces a change in macrophage phenotype from M1 into M2, and that the phenomenon is related to phosphorylation of transcription factor STAT3 and IL-10.
Authors: Irma Martha Medina-Díaz; Néstor Ponce-Ruíz; Aurora Elizabeth Rojas-García; José Francisco Zambrano-Zargoza; Yael Y Bernal-Hernández; Cyndia Azucena González-Arias; Briscia S Barrón-Vivanco; José Francisco Herrera-Moreno Journal: Antioxidants (Basel) Date: 2022-03-31