Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9989734 | Neurobiology of Disease | 2005 | 8 Pages |
Abstract
Activated microglia produce superoxide anion (O2â) 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 O2â and NO production. LAP-TGFβ1 was present in the Hippocampal-Cm as shown by immunoblot and a TGFβ1-dependent proliferation-inhibition bioassay. LAP-TGFβ1 and TGFβ activity increased in hippocampal cultures exposed to proinflammatory conditions (LPS and Interferon-gamma). The inhibition of O2â and NO production by Hippocampal-Cm was mimicked by the addition of recombinant TGFβ1. Treating Hippocampal-Cm with an antibody against TGFβ1 to neutralize its activity eliminated its ability to inhibit O2â and NO production. Our findings suggest that the TGFβ1 secreted by hippocampal cells modulated microglial activity. We propose that in pathological conditions, impairment of this modulatory mechanism could enhance microglia-mediated neurotoxicity.
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Authors
Rodrigo Herrera-Molina, Rommy von Bernhardi,