Regulation of tumor necrosis factor expression in a macrophage-like cell line by lipopolysaccharide and cyclic AMP
1989; Elsevier BV; Volume: 120; Issue: 2 Linguagem: Inglês
10.1016/0008-8749(89)90198-6
ISSN1090-2163
AutoresSteven M. Taffet, Kenneth J. Singhel, Julie F. Overholtzer, Sheila Shurtleff,
Tópico(s)Antimicrobial Peptides and Activities
ResumoBacterial lipopolysaccharide (LPS, 1 μg/ml) induced the rapid production of tumor necrosis factor (TNF-α) mRNA in the RAW264 macrophage-like cell line. TNF-α mRNA peaked within 45 min of LPS treatment and remained high for greater than 3 hr. Transcription of TNF-α mRNA was increased within 15 min of LPS treatment. The quantity of TNF-α mRNA in LPS-stimulated cells was reduced to basal levels by treatment with cAMP, cAMP analogs, or agents which raise intracellular cAMP. This was not a general effect on all mRNA levels as the expression of a second gene, ornithine decarboxylase, was enhanced by cAMP treatment. cAMP did not have an effect on the stability of TNF-α mRNA. This is in contrast to the protein synthesis inhibitor, cycloheximide, which leads to a stabilization of TNF-α mRNA. Our results suggest that the primary regulation of tumor necrosis factor by cAMP and LPS occurs at the transcriptional level.
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