Dual role of hypoxia-inducible factor 1 α in experimental pulmonary tuberculosis: its implication as a new therapeutic target. (31st May 2018)

• Record Type: Journal Article
• Authors: Baay-Guzman, Guillermina J; Duran-Padilla, Marco A; Rangel-Santiago, Jesus; Tirado-Rodriguez, Belen; Antonio-Andres, Gabriela; Barrios-Payan, Jorge; Mata-Espinosa, Dulce; Klunder-Klunder, Miguel; Vega, Mario I; Hernandez-Pando, Rogelio; Huerta-Yepez, Sara
• Is Part Of: Future microbiology. Volume 13:Number 7(2018)
• Page Start: 785
• Page End: 798
• Publication Date: 2018-05-31
• Subjects: 2-ME -- apoptosis -- Bid -- digital pathology -- HIF-1α -- pulmonary tuberculosis; Microbiology -- Research -- Periodicals; 616.9041
• DOI: 10.2217/fmb-2017-0168
• Languages: English
• ISSNs: 1746-0913

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.