| Full text | |
| Author(s): |
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
|
| Affiliation: | [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 |
| Abstract | |
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: | 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 Opportunities: | Scholarships in Brazil - Master |
| 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 Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense |
| Grantee: | Regina Pekelmann Markus |
| Support Opportunities: | Research Projects - Thematic Grants |