Nuclear Factor-κB-Independent Regulation of Lipopolysaccharide-Mediated Interleukin-6 Biosynthesis

Abstract

The possible involvement of nuclear factor (NF)-κB 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 μM) did not affect LPS-mediated IL-6 secretion. Whereas the selective inhibition of the NF-κB pathway by the action of caffeic acid phenyl ethyl ester (CAPE; 1–100 μM) attenuated LPS-dependent IL-6 production at 100 μM, sulfasalazine (SSA; 0.1–10 mM), a potent and irreversible inhibitor of NF-κB, did not inhibit LPS-dependent IL-6 secretion. Incorporation of a selectively permeant inhibitor of NF-κB, 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, did not reduce LPS-mediated release of IL-6. These data indicate a NF-κB-independent pathway mediating LPS-dependent regulation of IL-6 biosynthesis in the airway epithelium.