STAT1‐NFκB crosstalk triggered by interferon gamma regulates noradrenaline‐induced pineal hormonal production. Issue 3 (1st September 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of pineal research. Volume 67:Issue 3(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-09-01
• Subjects: IFN‐γ -- immune‐pineal axis -- inflammation -- melatonin -- pineal gland; Pineal gland -- Periodicals; Pineal Gland -- Periodicals; Épiphyse (Glande); Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 612.492
• DOI: 10.1111/jpi.12599
• Languages: English
• ISSNs: 0742-3098

Abstract

Abstract: 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.