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

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 exp...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 2010-11, Vol.45 (3), p.234-244
Main Authors: Veroni, Caterina, Gabriele, Lucia, Canini, Irene, Castiello, Luciano, Coccia, Eliana, Remoli, Maria Elena, Columba-Cabezas, Sandra, Aricò, Eleonora, Aloisi, Francesca, Agresti, Cristina
Format: Article
Language:English
Subjects:
Adrenomedullin
Animals
Cells, Cultured
Cytokine receptors
Cytokines
Gene Expression Regulation
Glial cells
Granulocyte Colony-Stimulating Factor - metabolism
Inflammation
Inflammation - immunology
Interferon-gamma - immunology
Interleukin-10 - metabolism
Mice
Microarray Analysis
Microarrays
Microglia - cytology
Microglia - metabolism
Receptors, Tumor Necrosis Factor, Type I - genetics
Receptors, Tumor Necrosis Factor, Type I - metabolism
Receptors, Tumor Necrosis Factor, Type II - genetics
Receptors, Tumor Necrosis Factor, Type II - metabolism
Signal Transduction - physiology
Tumor Necrosis Factor-alpha - metabolism
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Summary: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-γ 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.
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2010.06.014