Nuclear factor (NF)-kappa B blockade attenuates but does not abrogate LPS-mediated interleukin (IL)-1 beta biosynthesis in alveolar epithelial cells.
The role that the nuclear factor (NF)-kappa B plays in regulating the biosynthesis of interleukin (IL)-1 beta, an inflammatory cytokine, has been investigated in vitro. Irreversible inhibition of the proteasome complex by carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132; 1-50 microM) had no inhibitory effect on lipopolysaccharide (LPS)-mediated IL-1 beta biosynthesis. Furthermore, selective inhibition of NF-kappa B 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-kappa B, partially attenuated but did not abolish LPS-dependent IL-1 beta secretion. Incorporation of a selectively permeant inhibitor of NF-kappa B, SN-50 (1-20 microM), a peptide which contains the nuclear localization sequence (NLS) for the p50 NF-kappa B 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 IL-1 beta. It is concluded that the NF-kapp B pathway is partially implicated and its blockade attenuates but does not abrogate LPS-dependent IL-1 beta biosynthesis in alveolar epithelial cells.
Haddad
John J
JJ
Oxygen Signaling Group, Center for Research into Human Development, Tayside Institute of Child Health, Faculty of Medicine, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK [corrected]. johnjhaddad@yahoo.co.uk
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005333:Fetus; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis*; D007976:Leupeptins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D046988:Proteasome Endopeptidase Complex; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000196:embryology / Q000276:immunology*; D012460:Sulfasalazine / Q000494:pharmacology
D015853:Cysteine Proteinase Inhibitors; D007375:Interleukin-1; D007976:Leupeptins; D008070:Lipopolysaccharides; D009097:Multienzyme Complexes; D016328:NF-kappa B; D012460:Sulfasalazine; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde