Lipopolysaccharide stimulates phosphorylation of eukaryotic initiation factor-4F in macrophages and tumor necrosis...

Bacterial lipopolysaccharide (LPS) produces rapid changes in macrophage protein synthesis and function. Phosphorylation of the 25 kDa mRNA cap-binding protein (eIF-4E) in model systems regulates the efficiency of protein synthesis. We report that both LPS and tumor necrosis factor-alpha (TNF-alpha) stimulate phosphorylation of eIF-4E and the p220 component of eIF-4F in bone marrow-derived macrophages. Moreover, anti-TNF-alpha antibodies inhibit LPS-stimulated phosphorylation of eIF-4E and p220 by 43% (+/- 6%) and 50% (+/- 5%), respectively. Our results indicate that LPS stimulates eIF-4F phosphorylation by a TNF-alpha-dependent mechanism, and suggest that phosphorylation of eIF-4F might play a role in the post-transcriptional regulation of gene expression in macrophages exposed to LPS.