Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells

Glia. 1993 Mar;7(3):225-36. doi: 10.1002/glia.440070306.


In this report, we show that in the human astroglioma cell line D54-MG, both interleukin-1 (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) enhance C3 gene expression in a time- and dose-dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30-fold and 20-fold in response to IL-1 beta or TNF-alpha, respectively. C3 protein production increases proportionally, reaching levels 36-fold and 18-fold higher than untreated controls upon exposure to IL-1 beta or TNF-alpha, respectively. D54-MG cells require a minimal 1 h exposure to IL-1 beta in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF-alpha. Simultaneous treatment of D54-MG cells with IL-1 beta and interferon-gamma (IFN-gamma) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF-alpha and IFN-gamma. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL-1 beta (5.3-fold increase) and TNF-alpha (7-fold increase), while an additive effect was observed upon simultaneous treatment with both IL-1 beta and IFN-gamma. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN-gamma, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytoma / pathology*
  • Brain Neoplasms / pathology*
  • Complement C3 / biosynthesis*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Rats
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Proteins
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Complement C3
  • Interleukin-1
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma