Dual role of hypoxia-inducible factor 1 α in experimental pulmonary tuberculosis: its implication as a new therapeutic target

被引：27

作者：

Baay-Guzman, Guillermina J. ^{[1
]}

Duran-Padilla, Marco A. ^{[2
]}

Rangel-Santiago, Jesus ^{[1
]}

Tirado-Rodriguez, Belen ^{[1
]}

Antonio-Andres, Gabriela ^{[1
]}

Barrios-Payan, Jorge ^{[3
]}

Mata-Espinosa, Dulce ^{[3
]}

Klunder-Klunder, Miguel ^{[4
]}

Vega, Mario I. ^{[5
,6
]}

Hernandez-Pando, Rogelio ^{[3
]}

Huerta-Yepez, Sara ^{[1
]}

机构：

[1] Hosp Infantil Mexico Dr Federico Gomez, Feder Gomez, Unidad Invest Enfermedades Oncol, Mexico City, DF, Mexico

[2] Hosp Gen Mexico City, Serv Patol, Fac Med UNAM, Mexico City, DF, Mexico

[3] Natl Inst Med Sci & Nutr Salvador Zubiran, Sect Expt Pathol, Mexico City, DF, Mexico

[4] Hosp Infantil Mexico Dr Federico Gomez, Feder Gomez, Dept Invest Salud Comunitaria, Mexico City, DF, Mexico

[5] Oncol Hosp, CMN SXXI, IMSS, Oncol Res Unit, Mexico City, DF, Mexico

[6] Jonsson Comprehens Canc Ctr, UCLA Med Ctr, VA West Angeles Med Ctr BBRI, Dept Med,Hematol Oncol Div, Los Angeles, CA 90034 USA

来源：

FUTURE MICROBIOLOGY | 2018年 / 13卷 / 07期

关键词：

2-ME; apoptosis; Bid; digital pathology; HIF-1; alpha; pulmonary tuberculosis; MURINE MODEL; HIF-1-ALPHA; APOPTOSIS; GROWTH; NECROSIS; CELLS; LOCALIZATION; MACROPHAGE; EXPRESSION; YIN-YANG-1;

D O I：

10.2217/fmb-2017-0168

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Aim: Investigate the role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in pulmonary tuberculosis (TB). Methods & results: A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1 alpha expression was observed during early TB in activated macrophages. During late TB, even higher HIF-1 alpha expression was observed in foamy macrophages, which are resistant to apoptosis. Blocking HIF-1 alpha during early infection with 2-methoxyestradiol worsened the disease, while during late TB, it induced macrophage apoptosis and decreased bacillary loads. Conclusion: HIF-1 alpha 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.

引用

页码：785 / 798

页数：14

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