Open AccessExpression of the NF‐κB inhibitor ABIN‐3 in response to TNF and toll‐like receptor 4 stimulation is itself regulated by NF‐κB
Author(s) -
Verstrepen Lynn,
AdibConquy Minou,
Kreike Marja,
Carpentier Isabelle,
Adrie Christophe,
Cavaillon JeanMarc,
Beyaert Rudi
Publication year - 2007
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2007.00187.x
Subject(s) - nf κb , tumor necrosis factor alpha , toll like receptor , receptor , signal transduction , microbiology and biotechnology , chemistry , biology , innate immune system , immunology , biochemistry
Although the nuclear factor‐κB (NF‐κB)‐dependent gene expression is critical to the induction of an efficient immune response to infection or tissue injury, excessive or prolonged NF‐κB signalling can contribute to the development of several inflammatory diseases. Therefore, the NF‐κB signal transduction pathway is tightly regulated by several intracellular proteins. We have previously identified A20‐binding inhibitor of NF‐κB activation (ABIN)‐3 as an lipopolysaccharide (LPS)‐inducible protein in monocytes that negatively regulates NF‐B activation in response to tumour necrosis factor (TNF) and LPS. Here we report that ABIN‐3 expression is also up‐regulated upon TNF treatment of monocytes and other non‐myeloid cell types. We also found a significantly enhanced expression of ABIN‐3 in monocytes of sepsis patients, which is restored to control levels by corticotherapy. To further understand the transcriptional regulation of ABIN‐3 expression, we isolated the human ABIN‐3 promoter and investigated its activation in response to TNF and LPS. This revealed that the LPS‐ and TNF‐inducible expression of ABIN‐3 is dependent on the binding of NF‐κB to a specific B site in the ABIN‐3 promoter. Altogether, these data indicate an important role for NF‐κB‐dependent gene expression of ABIN‐3 in the negative feedback regulation of TNF receptor and toll‐like receptor 4 induced NF‐κB activation.