Interferon Regulatory Factor 1 Is an Essential and Direct Transcriptional Activator for Interferon γ-induced RANTES/CCl5 Expression in Macrophages*

Interferon regulatory factor 1 (IRF-1) is an important transcription factor in interferon γ (IFNγ)-mediated signaling in the development and function of NK cells and cytotoxic T lymphocytes. RANTES (regulated on activation normal T cell expressed and secreted; CCL5) is a member of the CC chemokine family of proteins, which is strongly chemoattractant for several important immune cell types in host defense against infectious agents and cancer. However, the role of IFNγ and IRF-1 in the regulation of RANTES gene expression and their operative mechanisms in macrophages have not been established. We report here that RANTES expression in IRF-1-null mice, primarily in macrophages, in response to carcinogenic stimulation in vivo and in vitro and to IFNγ but not to lipopolysaccharide in vitro, was markedly decreased. As a result, RANTES-mediated chemoattraction of CCR5+ target cells was also severely impaired. Adenovirus-mediated gene transduction of IRF-1 in primary macrophages resulted in enhanced RANTES expression. The IFNγ and IRF1 response element was localized to a TTTTC motif at –147 to –143 of the mouse RANTES promoter, to which endogenous or recombinant IRF-1 can physically bind in vitro and in vivo. This study uncovers a novel IFNγ-induced pathway in RANTES expression mediated by IRF-1 in macrophages and elucidates an important host defense mechanism against neoplastic transformation.

• Publication year

  2005

• Venue

  Journal of Biological Chemistry

• Publication date

  2005-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M500973200PMID 15860458
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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