title: Transforming growth factor-beta 1 produced by hippocampal cells modulates microglial reactivity in culture.
abstract: Activated microglia produce superoxide anion (O2-) and nitric oxide (NO), both of which can be neurotoxic. To identify regulatory mechanisms that might modulate over-activation of microglia, we evaluated the inhibition of microglial activation by factors secreted by hippocampal cells. Supernatants from hippocampal cell cultures (Hippocampal-Cm) prevented microglial O2- and NO production. LAP-TGF beta1 was present in the Hippocampal-Cm as shown by immunoblot and a TGF beta1-dependent proliferation-inhibition bioassay. LAP-TGF beta1 and TGFbeta activity increased in hippocampal cultures exposed to proinflammatory conditions (LPS and Interferon-gamma). The inhibition of O2- and NO production by Hippocampal-Cm was mimicked by the addition of recombinant TGF beta1. Treating Hippocampal-Cm with an antibody against TGF beta1 to neutralize its activity eliminated its ability to inhibit O2- and NO production. Our findings suggest that the TGF beta1 secreted by hippocampal cells modulated microglial activity. We propose that in pathological conditions, impairment of this modulatory mechanism could enhance microglia-mediated neurotoxicity.
authors.affiliation: Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Herrera-Molina
authors.forename: Rommy
authors.initials: R
authors.lastname: von Bernhardi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D017628:Microglia / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1