Journal
NEUROBIOLOGY OF DISEASE
Volume 19, Issue 1-2, Pages 229-236Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2005.01.003
Keywords
cytokines; hippocampal cell; inflammation; microglial cells; neurodegeneration; nitric oxide; superoxide anion; TGF beta 1
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available