Guillermina J Baay-Guzman1, Marco A Duran-Padilla2, Jesus Rangel-Santiago1, Belen Tirado-Rodriguez1, Gabriela Antonio-Andres1, Jorge Barrios-Payan3, Dulce Mata-Espinosa3, Miguel Klunder-Klunder4, Mario I Vega5,6, Rogelio Hernandez-Pando3, Sara Huerta-Yepez1. 1. Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City, Mexico. 2. Servicio de Patologia del Hospital General de Mexico, Facultad de Medicina de la UNAM, Mexico City, Mexico. 3. Section of Experimental Pathology, National Institute of Medical Sciences & Nutrition 'Salvador Zubirán', Mexico City, Mexico. 4. Departamento de Investigación en Salud Comunitaria, Hospital Infantil de Mexico, Federico Gomez, Mexico City, Mexico. 5. Oncology Research Unit, Oncology Hospital, CMN SXXI, IMSS, Mexico City, Mexico. 6. Department of Medicine, Hematology-Oncology Division, VA West Los Angeles Medical Center BBRI, UCLA Medical Center, Jonsson Comprehensive Cancer Center, Los Angeles, California, USA.
Abstract
AIM: Investigate the role of hypoxia-inducible factor-1α (HIF-1α) in pulmonary tuberculosis (TB). METHODS & RESULTS: A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1α expression was observed during early TB in activated macrophages. During late TB, even higher HIF-1α expression was observed in foamy macrophages, which are resistant to apoptosis. Blocking HIF-1α during early infection with 2-methoxyestradiol worsened the disease, while during late TB, it induced macrophage apoptosis and decreased bacillary loads. CONCLUSION: HIF-1α has a dual role in experimental TB. This finding could have therapeutic implications because combined treatment with 2-methoxyestradiol and antibiotics appeared to eliminate mycobacteria more efficiently than conventional chemotherapy during advanced disease.
AIM: Investigate the role of hypoxia-inducible factor-1α (HIF-1α) in pulmonary tuberculosis (TB). METHODS & RESULTS: A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1α expression was observed during early TB in activated macrophages. During late TB, even higher HIF-1α expression was observed in foamy macrophages, which are resistant to apoptosis. Blocking HIF-1α during early infection with 2-methoxyestradiol worsened the disease, while during late TB, it induced macrophage apoptosis and decreased bacillary loads. CONCLUSION: HIF-1α has a dual role in experimental TB. This finding could have therapeutic implications because combined treatment with 2-methoxyestradiol and antibiotics appeared to eliminate mycobacteria more efficiently than conventional chemotherapy during advanced disease.
Entities:
Keywords:
2-ME; Bid; HIF-1α; apoptosis; digital pathology; pulmonary tuberculosis
Authors: Mario I Vega; Yijiang Shi; Patrick Frost; Sara Huerta-Yepez; Gabriela Antonio-Andres; Rogelio Hernandez-Pando; Jihye Lee; Michael E Jung; Joseph F Gera; Alan Lichtenstein Journal: Mol Cancer Ther Date: 2019-08-08 Impact factor: 6.261
Authors: Aline de Oliveira Rezende; Rafaella Santos Sabóia; Adeliane Castro da Costa; Diana Messala Pinheiro da Silva Monteiro; Adrielle Zagmignan; Luis Ângelo Macedo Santiago; Rafael Cardoso Carvalho; Paulo Vitor Soeiro Pereira; Ana Paula Junqueira-Kipnis; Eduardo Martins de Sousa Journal: Biomedicines Date: 2022-03-31