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.
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| http://dx.doi.org/10.2217/fmb-2017-0168 | DOI Listing |
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