title: Activation of TNF receptor 2 in microglia promotes induction of anti-inflammatory pathways.
abstract: 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.
authors.affiliation: Departments of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Veroni
authors.forename: Lucia
authors.initials: L
authors.lastname: Gabriele
authors.forename: Irene
authors.initials: I
authors.lastname: Canini
authors.forename: Luciano
authors.initials: L
authors.lastname: Castiello
authors.forename: Eliana
authors.initials: E
authors.lastname: Coccia
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Remoli
authors.forename: Sandra
authors.initials: S
authors.lastname: Columba-Cabezas
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aricò
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
authors.forename: Cristina
authors.initials: C
authors.lastname: Agresti
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma