Nuclear factor-kappa B-independent regulation of lipopolysaccharide-mediated interleukin-6 biosynthesis.
The possible involvement of nuclear factor (NF)-kappa B in mediating the regulation of interleukin (IL)-6 biosynthesis in response to E. coli-derived lipopolysaccharide-endotoxin (LPS) was investigated in vitro. In alveolar epithelial cells, irreversible inhibition of the proteasome complex by carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132; 1-50 muM) did not affect LPS-mediated IL-6 secretion. Whereas the selective inhibition of the NF-kappa B pathway by the action of caffeic acid phenyl ethyl ester (CAPE; 1-100 microM) attenuated LPS-dependent IL-6 production at 100 muM, sulfasalazine (SSA; 0.1--10 mM), a potent and irreversible inhibitor of NF-kappa B, did not inhibit LPS-dependent IL-6 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, did not reduce LPS-mediated release of IL-6. These data indicate a NF-kappa B-independent pathway mediating LPS-dependent regulation of IL-6 biosynthesis in the airway epithelium.
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
Fahlman
Christian S
CS
D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000096:biosynthesis*; D007976:Leupeptins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology*; D012460:Sulfasalazine / Q000494:pharmacology
D002109:Caffeic Acids; D015853:Cysteine Proteinase Inhibitors; D015850:Interleukin-6; D007976:Leupeptins; D008070:Lipopolysaccharides; D009097:Multienzyme Complexes; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D012460:Sulfasalazine; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde