Expression of Cytokines by Human Astrocytomas Following Stimulation by C3a and C5a Anaphylatoxins
- 1 June 1999
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 72 (6), 2426-2436
- https://doi.org/10.1046/j.1471-4159.1999.0722426.x
Abstract
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)-1β, IL-6, tumor necrosis factor-α, and transforming growth factor-β mRNA expression was studied by quantitative RT-PCR. Whereas IL-1β, tumor necrosis factor-α, and transforming growth factor-β 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.This publication has 39 references indexed in Scilit:
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