The Role of High Mobility Group Box 1 Protein (HMGB1) in the Immunopathology of Experimental Pulmonary Tuberculosis

Background The high mobility group box 1 (HMGB1) is the prototype of alarmin protein released by stressed or dying cells. The redox state of this protein confers different functions in the regulation of inflammation and immune response. Aim Determine the kinetics, cellular sources and funct...

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Detalles Bibliográficos
Autores principales: Hernández-Pando, Rogelio, Barrios-Payán, Jorge, Mata-Espinosa, Dulce, Marquina-Castillo, Brenda, Hernández-Ramírez, Diego, Bottasso, Oscar, Bini, Estela Isabel
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: PLOS (Public Library of Science) 2015
Materias:
Antibodies
Inflammation
Cytokines
Macrophages
Mycobacterium tuberculosis
Immunostaining
Enzyme-linked immunoassays
Acceso en línea:http://hdl.handle.net/2133/4868
http://hdl.handle.net/2133/4868
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
Descripción
Sumario:Background The high mobility group box 1 (HMGB1) is the prototype of alarmin protein released by stressed or dying cells. The redox state of this protein confers different functions in the regulation of inflammation and immune response. Aim Determine the kinetics, cellular sources and function of HMGB1 in experimental tuberculosis. Methods BALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv. At different time points, HMGB1 was quantified in bronchial lavage fluid (BALF) and in lungs was determined its cellular sources by immunohistochemistry. HMGB1 was blocked with specific antibodies or recombinant HMGB1 was administered during early or late infection. Bacilli burdens, inflammation and cytokines expression were determined. Results The maximal concentration of HMGB1 in BALF was at day one of infection. Bronchial epithelium and macrophages were the most important sources. At day 7 to 21 the oxidized HMGB1 was predominant, while during late infection only the reduced form was seen. Blocking HMGB1 during early infection produced significant decrease of bacilli burdens and high production of pro-inflammatory cytokines, while the opposite was seen when HMGB1 was administered. Blocking HMGB1 activity or administrated it in high amounts during late infection worsening the disease. Conclusions HMGB1 is liberated during experimental tuberculosis and promotes or suppress the immune response and inflammation depending on the redox state.

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