Nuclear Factor-κB Blockade Attenuates but Does Not Abrogate Lipopolysaccharide-Dependent Tumor Necrosis Factor-α Biosynthesis in Alveolar Epithelial Cells

We have investigated the role that the nuclear factor (NF)-κB plays in regulating the biosynthesis of tumor necrosis factor (TNF)-α, an inflammatory cytokine. Irreversible inhibition of the proteasome complex by carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132; 1-50 μM) had no inhibitory effect on LPS-mediated TNF-α biosynthesis. Furthermore, selective inhibition of NF-κB by the action of caffeic acid phenylethyl ester (CAPE; 1-100 μM) and sulfasalazine (SSA; 0.1-10 μM), a potent and irreversible inhibitor of NF-κB, partially attenuated, but did not abolish, LPS-dependent TNF-α secretion. Incorporation of a selectively permeant inhibitor of NF-®B, SN-50 (1-20 μM), a peptide which contains the nuclear localization sequence (NLS) for the p50 NF-κB 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-α It is concluded that the NF-κB pathway is partially implicated and that its blockade attenuates, but does not abrogate, LPS-dependent TNF-α biosynthesis in alveolar epithelial cells.