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Nuclear factor-kappab blockade attenuates but does not abrogate lipopolysaccharide-dependent tumor necrosis factor-alpha biosynthesis in alveolar epithelial cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2001 Jul 13; Vol. 285 (2), pp. 267-72. - Publication Year :
- 2001
-
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.<br /> (Copyright 2001 Academic Press.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 285
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 11444836
- Full Text :
- https://doi.org/10.1006/bbrc.2001.5172