The IkappaB protein Bcl-3 negatively regulates transcription of the IL-10 gene in macrophages

J Immunol. 2005 Sep 15;175(6):3560-8. doi: 10.4049/jimmunol.175.6.3560.


NF-kappaB/Rel transcription factors, implicated in inflammatory and immune responses against pathogens, are regulated by IkappaB proteins. The physiological and molecular function of the IkappaB family member Bcl-3 is understood only poorly. In this study, the role of Bcl-3 in an innate immune response was examined by gene targeting. We demonstrate that Bcl-3(-/-) mice are highly susceptible to Listeria monocytogenes infection. This correlates with diminished production of IL-12 p70 and IFN-gamma in vivo, which is mainly due to elevated synthesis of IL-10. Isolated peritoneal macrophages from Bcl-3(-/-) mice also produce elevated amounts of IL-10, which inhibit IL-12 p70 synthesis in an autocrine fashion. Thus, these data establish Bcl-3 as an inhibitor of IL-10 expression in macrophages. Furthermore, we show that Bcl-3 is not implicated in IL-10 mRNA stabilization but regulates the initiation of IL-10 transcription. Taken together, our results show that an essential function of Bcl-3 during an innate immune response against bacteria is to inhibit transcription of the IL-10 gene in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Lymphoma 3 Protein
  • Down-Regulation*
  • I-kappa B Proteins / physiology
  • Immunity, Innate
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / genetics*
  • Interleukin-12 / biosynthesis
  • Listeriosis / immunology
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Knockout
  • Protein Subunits / biosynthesis
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / physiology*
  • RNA Stability
  • Transcription Factors
  • Transcription, Genetic*


  • B-Cell Lymphoma 3 Protein
  • Bcl3 protein, mouse
  • I-kappa B Proteins
  • Protein Subunits
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma