title: Interleukin-1beta and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes.
abstract: C3a and C5a anaphylatoxins are proinflammatory polypeptides released during complement activation. They exert their biological activities through interaction with two G protein-coupled receptors named C3aR and C5aR, respectively. In the brain, these receptors are expressed on glial cells, and some recent data have suggested that anaphylatoxins could mediate neuroprotection. In this study, we used RT-PCR and ribonuclease protection assays (RPA) to investigate the role of anaphylatoxins on neurotrophin expression by the human glioblastoma cell line T98G and by rat astrocytes. Our data show that for both cell types, anaphylatoxins upregulate expression of NGF mRNA. This response depended on a G protein-coupled pathway since pre-treatment of cells with pertussis toxin (PTX) completely blocked NGF mRNA increases. This effect was anaphylatoxin-specific since pre-incubation with anti-C3a or anti-C5aR antibodies abolished the effects of C3a and C5a, respectively. The regulation of NGF mRNA by anaphylatoxins was not accompanied by translation into protein expression, but there was a significant synergic effect of anaphylatoxins/IL-1b costimulation. Our demonstration of involvement of anaphylatoxins in the NGF release process by astrocytes suggests that C3a and C5a could modulate neuronal survival in the CNS.
authors.affiliation: Institut Fédératif de Recherche Multidisciplinaire sur les Peptides no23, INSERM U413, Faculté des Sciences, 76130 Mont-St-Aignan, France. acjauneau@hotmail.com
authors.forename: Anne-christine
authors.initials: AC
authors.lastname: Jauneau
authors.forename: Alexander
authors.initials: A
authors.lastname: Ischenko
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chatagner
authors.forename: Magalie
authors.initials: M
authors.lastname: Benard
authors.forename: Philippe
authors.initials: P
authors.lastname: Chan
authors.forename: Marie-therese
authors.initials: MT
authors.lastname: Schouft
authors.forename: Christine
authors.initials: C
authors.lastname: Patte
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Marc
authors.initials: M
authors.lastname: Fontaine