Lipopolysaccharide stimulates phosphorylation of eukaryotic initiation factor-4F in macrophages and tumor necrosis factor participates in this event.
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.
Haas
D W
DW
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Shepherd
V L
VL
Hagedorn
C H
CH
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008070:Lipopolysaccharides; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C075833:eIF-4