Regulation of IL-1 gene expression: differential responsiveness of murine macrophage lines

Cytokine. 1993 Jul;5(4):327-35. doi: 10.1016/1043-4666(93)90064-c.


In order to begin to define the mechanisms by which lipopolysaccharide (LPS) regulates IL-1 gene expression, we have examined IL-1 RNA levels, the transcription rate of the IL-1 genes, and IL-1 mRNA stabilities in P388D1/C, RAW264.7, and murine peritoneal exudate cells (PEC). These experiments showed that total cellular IL-1 RNA levels and IL-1 transcription rates were dramatically upregulated in all three cell types. In all cases, IL-1 alpha and IL-1 beta cellular RNA levels and gene transcription rates were regulated in parallel. However, the profiles of IL-1 gene activation during the 24 h after LPS treatment differed in these three cell types. Additionally, culture in the presence of actinomycin D (Act D) showed differential stabilities of the IL-1 alpha and IL-1 beta RNAs in these cells. In peritoneal exudate cells, the half-lives (t1/2) of the IL-1 alpha and IL-1 beta RNAs were each > 8 h. In RAW264.7 cells, the stability of the IL-1 beta RNA was greater than the IL-1 alpha RNA (t1/2 > 8 h and approximately 6 h, respectively). In P388D1/C cells, the t1/2's of the IL-1 alpha and beta RNAs varied depending on the time of addition of actinomycin D. This and other data suggest that components of the IL-1 RNA catabolic pathway are labile and sensitive to treatment with actinomycin D. Together these data indicate that the two IL-1 genes show a diverse regulatory repertoire, even within related mononuclear phagocytic cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / metabolism
  • Dactinomycin / pharmacology
  • Gene Expression Regulation* / drug effects
  • Interleukin-1 / biosynthesis*
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mice
  • Phagocytosis
  • RNA, Messenger / metabolism
  • Transcription, Genetic
  • Transcriptional Activation


  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Dactinomycin