Expression of cytokines by human astrocytomas following stimulation by C3a and C5a anaphylatoxins: specific increase in interleukin-6 mRNA expression

J Neurochem. 1999 Jun;72(6):2426-36. doi: 10.1046/j.1471-4159.1999.0722426.x.


C3a and C5a anaphylatoxins are two proinflammatory peptides generated during complement activation that act through distinct Gi protein-coupled receptors named C3aR and C5aR, respectively. We have demonstrated previously that human astrocytes expressed C3aR and C5aR constitutively and were able to produce a functional complement. In this study, we examined the effect of an anaphylatoxin stimulation on cytokine expression by human astrocyte cell lines. Interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, and transforming growth factor-beta mRNA expression was studied by quantitative RT-PCR. Whereas IL-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta mRNA levels remained unchanged, stimulation of astrocytoma cells (T98G, CB193, U118MG) by C3a, C5a, and peptidic C3aR and C5aR agonists induced an increase in the IL-6 mRNA level. The amount of IL-6 was markedly increased at 3 and 6 h and returned to the basal level at 9 h of stimulation. This response was specific, because pretreatment of cells with pertussis toxin or with polyclonal anti-C3aR or anti-C5aR antibodies completely blocked the IL-6 mRNA increase. The IL-6 response was also investigated at the protein level, but IL-6 protein was detected neither in cell lysates nor in supernatants of stimulated cells. The anaphylatoxin-mediated transcriptional activation of IL-6 gene suggests that C3a and C5a could play a role in priming glial cells during the inflammatory process in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylatoxins / pharmacology
  • Anaphylatoxins / physiology
  • Antibodies / pharmacology
  • Antigens, CD / physiology
  • Astrocytoma / immunology*
  • Complement C3a / pharmacology
  • Complement C3a / physiology*
  • Complement C5a / pharmacology
  • Complement C5a / physiology*
  • Cytokines / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-6 / genetics*
  • Kinetics
  • Membrane Proteins*
  • Pertussis Toxin
  • RNA, Messenger / genetics
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / immunology*
  • Transforming Growth Factor beta / genetics
  • Tumor Cells, Cultured
  • Virulence Factors, Bordetella / pharmacology


  • Anaphylatoxins
  • Antibodies
  • Antigens, CD
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Membrane Proteins
  • RNA, Messenger
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Transforming Growth Factor beta
  • Virulence Factors, Bordetella
  • complement C3a receptor
  • Complement C3a
  • Complement C5a
  • Pertussis Toxin