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STAT1‐NFκB crosstalk triggered by interferon gamma regulates noradrenaline‐induced pineal hormonal production
Author(s) -
Barbosa Lima Leila Eliza,
Muxel Sandra Marcia,
Kinker Gabriela S.,
CarvalhoSousa Cláudia Emanuele,
Silveira CruzMachado Sanseray,
Markus Regina P.,
Fernandes Pedro Augusto Carlos Magno
Publication year - 2019
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12599
Subject(s) - melatonin , stat1 , stat protein , transactivation , transcription factor , cytokine , biology , crosstalk , medicine , endocrinology , nf κb , microbiology and biotechnology , signal transduction , pineal gland , tumor necrosis factor alpha , cancer research , stat3 , immunology , biochemistry , gene , physics , optics
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.