1. Nuclear factor-kappab blockade attenuates but does not abrogate lipopolysaccharide-dependent tumor necrosis factor-alpha biosynthesis in alveolar epithelial cells.
- Author
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Haddad JJ and Land SC
- Subjects
- 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, Lipopolysaccharides pharmacology, NF-kappa B metabolism, Peptides pharmacology, Pulmonary Alveoli physiology, Respiratory Mucosa physiology, Tumor Necrosis Factor-alpha biosynthesis
- 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.)
- Published
- 2001
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