Modulation of interferon-γ-induced glial cell activation by transforming growth factor ß1: a role for STAT1 and MAPK pathways.
J Neurochem
; 123(1): 113-23, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22823229
Overactivated glial cells can produce neurotoxic oxidant molecules such as nitric oxide (NO·) and superoxide anion (O(2)·(-)). We have previously reported that transforming growth factor ß1 (TGFß1) released by hippocampal cells modulates interferon-γ (IFNγ)-induced production of O(2)·(-) and NO· by glial cells. However, underlying molecular mechanisms are not completely understood, thereby, the aim of this work was to study the effect of TGFß1 on IFNγ-induced signaling pathways. We found that costimulation with TGFß1 decreased IFNγ-induced phosphorylation of signal transducer and activator of transcription-type-1 (STAT1) and extracellular signal-regulated kinase (ERK), which correlated with a reduced O(2)·(-) and NO· production in mixed and purified glial cultures. Moreover, IFNγ caused a decrease in TGFß1-mediated phosphorylation of P38, whereas pre-treatment with ERK and P38 inhibitors decreased IFNγ-induced phosphorylation of STAT1 on serine727 and production of radical species. These results suggested that modulation of glial activation by TGFß1 is mediated by deactivation of MAPKs. Notably, TGFß1 increased the levels of MAPK phosphatase-1 (MKP-1), whose participation in TGFß1-mediated modulation was confirmed by MKP-1 siRNA transfection in mixed and purified glial cultures. Our results indicate that the cross-talk between IFNγ and TGFß1 might regulate the activation of glial cells and that TGFß1 modulated IFNγ-induced production of neurotoxic oxidant molecules through STAT1, ERK, and P38 pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuroglia
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Interferon gama
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Sistema de Sinalização das MAP Quinases
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Fator de Transcrição STAT1
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Fator de Crescimento Transformador beta1
Limite:
Animals
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Reino Unido