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Publication : Activation of TNF receptor 2 in microglia promotes induction of anti-inflammatory pathways.

First Author  Veroni C Year  2010
Journal  Mol Cell Neurosci Volume  45
Issue  3 Pages  234-44
PubMed ID  20600925 Mgi Jnum  J:171323
Mgi Id  MGI:4949600 Doi  10.1016/j.mcn.2010.06.014
Citation  Veroni C, et al. (2010) Activation of TNF receptor 2 in microglia promotes induction of anti-inflammatory pathways. Mol Cell Neurosci 45(3):234-44
abstractText  Fine regulation of the innate immune response following brain injury or infection is important to avoid excessive activation of microglia and its detrimental consequences on neural cell viability and function. To get insights on the molecular networks regulating microglia activation, we analyzed expression, regulation and functional relevance of tumor necrosis factor receptors (TNFR) 2 in cultured mouse microglia. We found that microglia upregulate TNFR2 mRNA and protein and shed large amounts of soluble TNFR2, but not TNFR1, in response to pro-inflammatory stimuli and through activation of TNFR2 itself. By microarray analysis, we demonstrate that TNFR2 stimulation in microglia regulates expression of genes involved in immune processes, including molecules with anti-inflammatory and neuroprotective function like granulocyte colony-stimulating factor, adrenomedullin and IL-10. In addition, we identify IFN-gamma as a regulator of the balance between pro- and anti-inflammatory/neuroprotective factors induced by TNFR2 stimulation. These data indicate that, through TNFR2, microglia may contribute to the counter-regulatory response activated in neuropathological conditions.
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