Nuclear factor-kappab blockade attenuates but does not abrogate lipopolysaccharide-dependent tumor necrosis factor-alpha biosynthesis in alveolar epithelial cells.

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  • Author(s): Haddad JJ;Haddad JJ; Land SC
  • Source:
    Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2001 Jul 13; Vol. 285 (2), pp. 267-72.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print Cited Medium: Print ISSN: 0006-291X (Print) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Lipopolysaccharides/*pharmacology ; NF-kappa B/*metabolism ; Peptides/*pharmacology ; Pulmonary Alveoli/*physiology ; Respiratory Mucosa/*physiology ; Tumor Necrosis Factor-alpha/*biosynthesis; Animals ; Dose-Response Relationship, Drug ; Fetus ; Kinetics ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/chemistry ; Protein Subunits ; Pulmonary Alveoli/cytology ; Pulmonary Alveoli/drug effects ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/pharmacology ; Respiratory Mucosa/cytology ; Respiratory Mucosa/drug effects
    • Abstract:
      We have investigated the role that the nuclear factor (NF)-kappaB plays in regulating the biosynthesis of tumor necrosis factor (TNF)-alpha, an inflammatory cytokine. Irreversible inhibition of the proteasome complex by carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (MG-132; 1-50 microM) had no inhibitory effect on LPS-mediated TNF-alpha biosynthesis. Furthermore, selective inhibition of NF-kappaB by the action of caffeic acid phenylethyl ester (CAPE; 1-100 microM) and sulfasalazine (SSA; 0.1-10 mM), a potent and irreversible inhibitor of NF-kappaB, partially attenuated, but did not abolish, LPS-dependent TNF-alpha secretion. Incorporation of a selectively permeant inhibitor of NF-kappaB, SN-50 (1-20 microM), a peptide which contains the nuclear localization sequence (NLS) for the p50 NF-kappaB subunit, and the amino-terminal sequence of Kaposi fibroblast growth factor to promote cell permeability, attenuated in a dose-dependent manner LPS-mediated release of TNF-alpha. It is concluded that the NF-kappaB pathway is partially implicated and that its blockade attenuates, but does not abrogate, LPS-dependent TNF-alpha biosynthesis in alveolar epithelial cells.
      (Copyright 2001 Academic Press.)
    • Accession Number:
      0 (Lipopolysaccharides)
      0 (NF-kappa B)
      0 (Peptides)
      0 (Protein Subunits)
      0 (Recombinant Proteins)
      0 (SN50 peptide)
      0 (Tumor Necrosis Factor-alpha)
    • Publication Date:
      Date Created: 20010711 Date Completed: 20010816 Latest Revision: 20061115
    • Publication Date:
      20221213
    • Accession Number:
      10.1006/bbrc.2001.5172
    • Accession Number:
      11444836