Essential roles for NF-kappa B and a Toll/IL-1 receptor domain-specific signal(s) in the induction of I kappa B-zeta

Biochem Biophys Res Commun. 2003 Feb 7;301(2):495-501. doi: 10.1016/s0006-291x(02)03082-6.

Abstract

I kappa B-zeta, a new negative-regulator of nuclear factor-kappa B (NF-kappa B), is strongly induced by lipopolysaccharide or interleukin-1 beta stimulation, but not by tumor necrosis factor-alpha. Here, we analyzed the mechanisms for transcriptional induction of I kappa B-zeta. I kappa B-zeta mRNA was induced by overexpression of MyD88 or TRAF6, but not TRAF2. Stimulation of macrophages with peptidoglycan or CpG DNA, which activated Toll-like receptor 2 or 9, respectively, also resulted in I kappa B-zeta induction. Thus, activation of the MyD88-dependent signaling pathway, commonly found downstream of different Toll/interleukin-1 receptor (TIR) domains, is sufficient for I kappa B-zeta induction. The induction was inhibited by treatment with various inhibitors of NF-kappa B activation or by overexpressing I kappa B-alpha or beta, indicating essential roles for NF-kappa B in I kappa B-zeta induction. However, overexpression of the NF-kappa B subunits induced I kappa B-alpha, but not I kappa B-zeta. These results indicate the existence of another signal essential for I kappa B-zeta induction, which is specifically mediated by the TIR domain-mediated signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Cell Line
  • CpG Islands
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drosophila Proteins*
  • Gene Expression Regulation
  • Genes, Reporter
  • Glucans / metabolism
  • Humans
  • I-kappa B Proteins
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Myeloid Differentiation Factor 88
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptidoglycan / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, Interleukin-1 / metabolism*
  • Signal Transduction / physiology*
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 2
  • Toll-Like Receptors

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Cysteine Proteinase Inhibitors
  • Drosophila Proteins
  • Glucans
  • I-kappa B Proteins
  • Lipopolysaccharides
  • MYD88 protein, human
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • NFKBIZ protein, human
  • Nfkbiz protein, mouse
  • Nuclear Proteins
  • Peptidoglycan
  • Protein Isoforms
  • Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • TLR2 protein, human
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 2
  • Toll-Like Receptors