Expression of Cytokines by Human Astrocytomas Following Stimulation by C3a and C5a Anaphylatoxins : Specific Increase in Interleukin-6 mRNA Expression

Sakina Sayah-Jeanne (1) , Alexander M. Ischenko (1) , Alexander Zhakhov (1) , Anne-Sophie Bonnard (1, 2) , Marc Fontaine (1)

1 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
2 U78 INSERM - Unité de Recherches sur la Génétique des Protéines Humaines [Bois-Guillaume]

C3a and C5a anaphylatoxins are two proinflammatory peptides generated during complement activation that act through distinct G$_i$ 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)-1$\beta$, IL-6, tumor necrosis factor-\alpha$, and transforming growth factor-$\beta$ mRNA expression was studied by quantitative RT-PCR. Whereas IL-1$\beta$, 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 antiC5aR 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

Mots clés: Complement; Anaphylatoxin; Astrocytes; Cytokines; Brain; Inflammation

Domaines: Immunologie; Neurosciences [q-bio.NC]

Sakina Sayah-Jeanne, Alexander M. Ischenko, Alexander Zhakhov, Anne-Sophie Bonnard, Marc Fontaine. Expression of Cytokines by Human Astrocytomas Following Stimulation by C3a and C5a Anaphylatoxins : Specific Increase in Interleukin-6 mRNA Expression. Journal of Neurochemistry, 1999, 72 (6), pp.2426-2436. ⟨10.1046/j.1471-4159.1999.0722426.x⟩. ⟨cea-02134831⟩