title: Role of type I interferon in the bacillus Calmette-Guérin-induced expression of CXCL10 from human monocytes.
abstract: BACKGROUND
  The proinflammatory chemokine CXCL10, in addition to its chemotactic properties, is also involved in the stimulation of natural killer and T-cell migration in Mycobacterium tuberculosis infection. In this study, our experiments were designed to determine the role of interferon (IFN)-alphabeta in the production of CXCL10 by human monocytes infected with Mycobacterium bovis bacillus Calmette-Guerin (BCG).
  
  
  METHODS
  The concentrations of CXCL10 in culture supernatants of monocytes infected with M. bovis BCG were determined by enzyme-linked immunosorbent assay. CXCL10 mRNA levels were determined by the reverse transcription-polymerase chain reaction method.
  
  
  RESULTS
  We have shown the induction of CXCL10 following infection with M. bovis BCG in a dose-dependent and time-dependent manner. Importantly, the secretion of CXCL10 in response to M. bovis was increased by IFN-alpha. These results were further confirmed by the fact that the addition of an anti-IFN-alphabeta neutralizing antibody completely reversed the stimulatory effect, whereas an isotype-matched control antibody had no significant effect on CXCL10 secretion. It is important to note that no significant effect of type I IFN on CXCL8 production in M. bovis-infected monocytes was observed. This was consistent with the finding by the reverse transcription-polymerase chain reaction method that treatment with anti-IFN-alpha/beta antibodies potentially inhibited CXCL10 mRNA levels, whereas no significant effect was observed on CXCL8 mRNA. Moreover, in THP-1 monocytes and THP-1 macrophages, the addition of exogenous IFN-alpha stimulated CXCL10 secretion.
  
  
  CONCLUSIONS
  Collectively, these results indicate that the type I IFN may play an important role to modulate the expression of CXCL10 in M. bovis BCG infection. Studies on M. bovis-induced chemokine secretion could provide important insight into the regulation of the immune response against tuberculosis.
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, México, D.F. 11340 México. pmendezs@bios.encb.ipn.mx
authors.forename: Patricia
authors.initials: P
authors.lastname: Méndez Samperio
authors.forename: Artemisa
authors.initials: A
authors.lastname: Trejo
authors.forename: Elena
authors.initials: E
authors.lastname: Miranda
mesh_terms: D000906:Antibodies / Q000008:administration & dosage; D002460:Cell Line; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000037:antagonists & inhibitors; D016899:Interferon-beta / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D000906:Antibodies; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D018836:Inflammation Mediators; D007370:Interferon Type I; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016899:Interferon-beta