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Expression of Cytokines by Human Astrocytomas Following Stimulation by C3a and C5a Anaphylatoxins
Author(s) -
Sayah Sakina,
Ischenko Alexander M.,
Zhakhov Alexander,
Bonnard AnneSophie,
Fontaine Marc
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722426.x
Subject(s) - anaphylatoxin , proinflammatory cytokine , tumor necrosis factor alpha , biology , astrocyte , complement system , cytokine , stimulation , interleukin , microbiology and biotechnology , immunology , endocrinology , inflammation , immune system , central nervous system
C3a and C5a anaphylatoxins are two proinflammatorypeptides generated during complement activation that act through distinctG 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)‐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.