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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 7
[1] Univ Sao Paulo, Inst Biosci, Dept Physiol, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Journal of Pineal Research; v. 67, n. 3 OCT 2019.
Web of Science Citations: 1

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)

FAPESP's process: 10/52687-1 - Characterization of the role of adrenal/pineal interaction in the immune-pineal axis context
Grantee:Pedro Augusto Carlos Magno Fernandes
Support type: Regular Research Grants
FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
Grantee:Regina Pekelmann Markus
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/09622-1 - Characterization of the molecular effects of interferon-gamma on the production of melatonin by rat pineal glands
Grantee:Leila Eliza Barbosa Lima
Support type: Scholarships in Brazil - Master