IL-1 and TNF-alpha induction of IL-8 and monocyte chemotactic and activating factor (MCAF) mRNA expression in a human astrocytoma cell line

Immunology. 1991 Sep;74(1):60-7.


In order to elucidate the role of inflammatory cytokines in the central nervous system (CNS), we examined whether IL and TNF-alpha induce cells in the CNS to produce two newly identified leucocyte chemo-attractants, IL-8 and monocyte chemotactic and activating factor (MCAF). Several human astrocytoma and glioblastoma cell lines expressed high levels of IL-8 and MCAF mRNA in vitro upon stimulation with IL-1 and TNF-alpha. In particular, an astrocytoma cell line U373MG subclone responded markedly to IL-1 with high expression levels of IL-8 and MCAF mRNA as well as IL-6 mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 and appeared as early as 30 min to 1 hr after IL-1 stimulation, confirming that these are early inducible genes. The production of IL-8 and MCAF in the U373MG cell culture supernatants was confirmed by a competitive radioimmunoassay (RIA) as well as chemotactic activities on human neutrophils and monocytes. IL-1-induced IL-8 and MCAF mRNA expression appeared to occur at least at the transcriptional level as revealed by a nuclear run-off assay. Moreover, IL-1 treatment increased the half-life of IL-8 and MCAF mRNA markedly, suggesting that increased mRNA stability was also responsible for the enhanced gene transcription. These data suggest that IL-1 and TNF-alpha induce astrocytes to produce IL-8 and MCAF transcriptionally and post-transcriptionally, both of which may be responsible for leucocytosis seen in inflammation of the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / immunology*
  • Cell Line
  • Chemokine CCL2
  • Chemotactic Factors / biosynthesis*
  • Chemotactic Factors / genetics
  • Dose-Response Relationship, Immunologic
  • Gene Expression Regulation
  • Humans
  • Interleukin-1 / pharmacology*
  • Interleukin-8 / genetics
  • Interleukin-8 / pharmacology*
  • RNA, Messenger / immunology
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Chemokine CCL2
  • Chemotactic Factors
  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha