Role of IKK1 and IKK2 in Lipopolysaccharide Signaling in Human Monocytic Cells*

Mononuclear phagocytes play a major role in immune and inflammatory responses. Bacterial lipopolysaccharide (LPS) induces monocytes to express a variety of genes by activating the NF-κB/Rel transcription factor family. Recently, we have reported that the tumor necrosis factor and interleukin 1 signaling pathways activate two kinases, IKK1 and IKK2. Phosphorylation of the IκB cytoplasmic inhibitors, IκBα, IκBβ, and IκBε, by these kinases triggers proteolytic degradation and the release of NF-κB/Rel proteins into the nucleus. At present, the role of the IKKs in LPS signaling has not been investigated. Here, we report that LPS induces IKK activity in human monocytes and THP-1 monocytic cells. The kinetics of activation of kinase activity in monocytic cells are relatively slow with maximal activity observed at 60 min, which coincides with the degradation of IκBs and the nuclear translocation of NF-κB. In transfection experiments, overexpression of wild type IKK1, a dominant negative mutant IKK1 (K44M), or wild type IKK2 did not affect LPS-induced κB-dependent transcription in monocytic cells. In contrast, a dominant negative mutant of IKK2 inhibited LPS induction of κB-dependent transcription in a dose-dependent manner. These results indicate that LPS induction of κB-dependent gene expression in human monocytic cells requires activation of IKK2.

• Publication year

  1998

• Venue

  Journal of Biological Chemistry

• Publication date

  1998-11-13

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.273.46.30410PMID 9804806
• 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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