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

• Published in: Journal of neurochemistry Vol. 72; no. 6; pp. 2426 - 2436
• Main Authors: SAYAH, S, ISCHENKO, A. M, ZHAKHOV, A, BONNARD, A.-S, FONTAINE, M
• Format: Journal Article
• Language: Russian; English
• Published: Oxford Blackwell 01.06.1999
• Subjects: anaphylatoxins; Anaphylatoxins - pharmacology; Anaphylatoxins - physiology; Antibodies - pharmacology; Antigens, CD - physiology; astrocytoma; 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; Receptor, Anaphylatoxin C5a; Receptors, Complement - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Time Factors; Transcription, Genetic - drug effects; Transcription, Genetic - immunology; Transforming Growth Factor beta - genetics; Tumor Cells, Cultured; Virulence Factors, Bordetella - pharmacology
• ISSN: 0022-3042; 1471-4159
• 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.