title: Role of cellular activation and tumor necrosis factor-alpha in the early expression of Mycobacterium tuberculosis 85B mRNA in human alveolar macrophages.
abstract: BACKGROUND
  Infection of alveolar macrophages (AMs), which constitute the first line of defense against Mycobacterium tuberculosis, initiates an intense interaction between the host's innate immune response and mycobacteria that may assist in the successful intracellular parasitism of M. tuberculosis.
  
  
  METHODS
  Expression of tumor necrosis factor (TNF)- alpha and M. tuberculosis 85B mRNA was studied in M. tuberculosis-infected AMs, to better delineate the role of macrophages in the early events in initiation of infection.
  
  
  RESULTS
  Both TNF- alpha mRNA and M. tuberculosis 85B were induced in AMs; at 24 h, the time point of maximum TNF- alpha induction, the mRNA levels for TNF- alpha and M. tuberculosis 85B correlated with one another, and induction of either gene correlated strongly with their protein levels. Inhibition of endogenous TNF- alpha by soluble (s) TNF receptor (R) I and sTNFRII reduced expression of both TNF- alpha and M. tuberculosis 85B. The activation of nuclear factor- kappa B was found to underlie expression of both TNF- alpha and M. tuberculosis 85B. Exogenous TNF- alpha was slightly more potent than interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor and was significantly stronger than IL-1 in inducing expression of M. tuberculosis 85B. Interestingly, inhibition of bactericidal mediators, reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates (RNIs), reduced expression of TNF- alpha and M. tuberculosis 85B genes in M. tuberculosis-infected AMs.
  
  
  CONCLUSIONS
  Activation of AMs by M. tuberculosis initiates a cascade of events whereby TNF- alpha, ROI, and RNI enhance the expression of the M. tuberculosis 85B gene.
authors.affiliation: Division of Infectious Disease, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Najmul
authors.initials: N
authors.lastname: Islam
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Kanost
authors.forename: Luciella
authors.initials: L
authors.lastname: Teixeira
authors.forename: John
authors.initials: J
authors.lastname: Johnson
authors.forename: Rana
authors.initials: R
authors.lastname: Hejal
authors.forename: Htin
authors.initials: H
authors.lastname: Aung
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Christina S
authors.initials: CS
authors.lastname: Hirsch
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toossi
mesh_terms: D000217:Acyltransferases / Q000032:analysis / Q000235:genetics*; D000328:Adult; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics*; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics*; D002478:Cells, Cultured; D000068800:Etanercept; D015964:Gene Expression Regulation, Bacterial; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1; D015850:Interleukin-6; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D016328:NF-kappa B / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis; D000068800:Etanercept