STAT1-NF kappa B crosstalk triggered by interferon gamma regulates noradrenaline-induced pineal hormonal production

Autor(es)

Barbosa Lima, Leila Eliza ^[1] ; Muxel, Sandra Marcia ^[1] ; Kinker, Gabriela S. ^[1] ; Carvalho-Sousa, Claudia Emanuele ^[1] ; Cruz-Machado, Sanseray da Silveira ^[1] ; Markus, Regina P. ^[1] ; Carlos Magno Fernandes, Pedro Augusto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biosci, Dept Physiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pineal Research; v. 67, n. 3 OCT 2019.
• Citações Web of Science: 1

Resumo

Melatonin production by pineal glands is modulated by several immune signals. The nuclear translocation of nuclear factor kappa-B (NF kappa B) 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-gamma), 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-gamma might also activate NF kappa B. The present study evaluated the role of STAT1-NF kappa B crosstalk triggered by IFN-gamma regarding the regulation of NA-induced pineal glands' hormonal production. Moreover, IFN-gamma 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-gamma induced the nuclear translocation of RelA-NF kappa B subunits. The blockade of this pathway prevented IFN-gamma effects on the pineal function. The present data show that STAT1 and NF kappa B crosstalk controls melatonin production through a synergistic mechanism, disclosing a new integrative mechanism regarding pineal hormonal activity control. (AU)

• Processo FAPESP: 10/52687-1 - Caracterização do papel da inter-relação adrenal-pineal no contexto do eixo imune-pineal
• Beneficiário: Pedro Augusto Carlos Magno Fernandes
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/13691-1 - Eixo imune-pineal: integrando a biologia do tempo em condições fisiológicas, fisiopatológicas e patológicas
• Beneficiário: Regina Pekelmann Markus
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/09622-1 - Caracterização dos efeitos moleculares do interferon-gama sobre a produção de melatonina por glândulas pineais de ratos
• Beneficiário: Leila Eliza Barbosa Lima
• Linha de fomento: Bolsas no Brasil - Mestrado