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STAT1-NFκB crosstalk triggered by interferon gamma regulates noradrenaline-induced pineal hormonal production.
Barbosa Lima, Leila Eliza; Muxel, Sandra Marcia; Kinker, Gabriela S; Carvalho-Sousa, Cláudia Emanuele; da Silveira Cruz-Machado, Sanseray; Markus, Regina P; Fernandes, Pedro Augusto Carlos Magno.
Afiliación
  • Barbosa Lima LE; Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
  • Muxel SM; Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
  • Kinker GS; Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
  • Carvalho-Sousa CE; Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
  • da Silveira Cruz-Machado S; Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
  • Markus RP; Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
  • Fernandes PACM; Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
J Pineal Res ; 67(3): e12599, 2019 Oct.
Article en En | MEDLINE | ID: mdl-31356684
Melatonin production by pineal glands is modulated by several immune signals. The nuclear translocation of nuclear factor kappa-B (NFκB) homodimers, lacking transactivation domains, once induced by lipopolysaccharide (LPS) or tumor necrosis factor (TNF), inhibits the expression of Aanat gene and the synthesis of noradrenaline (NA)-induced melatonin. Interferon gamma (IFN-γ), on the other hand, increases melatonin synthesis. Furthermore, this cytokine activates the signal transducer as well as the activator of transcription 1 (STAT1) pathway, which was never evaluated as a melatonin synthesis modulator before. Reports demonstrated that IFN-γ might also activate NFκB. The present study evaluated the role of STAT1-NFκB crosstalk triggered by IFN-γ regarding the regulation of NA-induced pineal glands' hormonal production. Moreover, IFN-γ treatment increased NA-induced Aanat transcription, in addition to the synthesis of N-acetylserotonin (NAS) and melatonin. These effects were associated with STAT1 nuclear translocation, confirmed by the co-immunoprecipitation of STAT1 and Aanat promoter. Pharmacological STAT1 enhancement augmented NA-induced Aanat transcription as well as NAS and melatonin production. Additionally, IFN-γ induced the nuclear translocation of RelA-NFκB subunits. The blockade of this pathway prevented IFN-γ effects on the pineal function. The present data show that STAT1 and NFκB crosstalk controls melatonin production through a synergistic mechanism, disclosing a new integrative mechanism regarding pineal hormonal activity control.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glándula Pineal / Norepinefrina / FN-kappa B / Interferón gamma / Factor de Transcripción STAT1 Límite: Animals Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Brasil

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glándula Pineal / Norepinefrina / FN-kappa B / Interferón gamma / Factor de Transcripción STAT1 Límite: Animals Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Brasil