Browsing by Author "Herrera Molina, R"

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    Transforming growth factor-beta 1 produced by hippocampal cells modulates microglial reactivity in culture
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2005) Herrera Molina, R; von Bernhardi, R
    Activated microglia produce superoxide anion (O-2(center dot-)) 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 O-2(center dot) and NO production. LAP-TGF beta 1 was present in the Hippocampal-Cm as shown by immunoblot and a TGF beta 1-dependent proliferation-inhibition bioassay. LAP-TGF beta 1 and TGF beta activity increased in hippocampal cultures exposed to proinflammatory conditions (LPS and Interferon-gamma). The inhibition of (O-2(center dot-)) and NO production by Hippocampal-Cm was mimicked by the addition of recombinant TGF beta 1. Treating Hippocampal-Cm with an antibody against TGF beta 1 to neutralize its activity eliminated its ability to inhibit O-2(center dot-) and NO production. Our findings suggest that the TGF beta 1 secreted by hippocampal cells modulated microglial activity. We propose that in pathological conditions, impairment of this modulatory mechanism could enhance microglia-mediated neurotoxicity. (c) 2005 Elsevier Inc. All rights reserved.