title: The Role of High Mobility Group Box 1 Protein (HMGB1) in the Immunopathology of Experimental Pulmonary Tuberculosis.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, 14000, México.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, 14000, México.
authors.forename: Jorge
authors.initials: J
authors.lastname: Barrios-Payán
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, 14000, México.
authors.forename: Dulce
authors.initials: D
authors.lastname: Mata-Espinosa
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, 14000, México.
authors.forename: Brenda
authors.initials: B
authors.lastname: Marquina-Castillo
authors.affiliation: Immunology Department, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, 14000, México.
authors.forename: Diego
authors.initials: D
authors.lastname: Hernández-Ramírez
authors.forename: Oscar Adelmo
authors.initials: OA
authors.lastname: Bottasso
authors.affiliation: Institute of Experimental and Clinic Immunology, Rosario, IDICER, CONICET, School of Medical Sciences, Santa Fe 3100, Rosario, 2000, Argentina.
authors.forename: Oscar Adelmo
authors.initials: OA
authors.lastname: Botasso
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, 14000, México; Institute of Experimental and Clinic Immunology, Rosario, IDICER, CONICET, School of Medical Sciences, Santa Fe 3100, Rosario, 2000, Argentina.
authors.forename: Estela Isabel
authors.initials: EI
authors.lastname: Bini
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D058491:Bacterial Load / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology; D010084:Oxidation-Reduction; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000906:Antibodies; D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse