褪黑素
内科学
内分泌学
NF-κB
车站3
松果体
生物
信号转导
促炎细胞因子
STAT蛋白
免疫系统
化学
细胞生物学
炎症
医学
免疫学
作者
Marlina Olyissa Córdoba-Moreno,Gabriela Christine Santos,Sandra Márcia Muxel,Débora dos Santos‐Silva,Caroline Luísa Quiles,Kassiano dos Santos Sousa,Regina P. Markus,Pedro Augusto Carlos Magno Fernandes
摘要
Abstract Immune‐pineal axis activation is part of the assembly of immune responses. Proinflammatory cytokines inhibit the pineal synthesis of melatonin while inducing it in macrophages by mechanisms dependent on nuclear factor‐κB (NF‐κB) activation. Cytokines activating the Janus kinase/signal transducer and activator of transcription (STAT) pathways, such as interferon‐gamma (IFN‐γ) and interleukin‐10 (IL‐10), modulate melatonin synthesis in the pineal, bone marrow (BM), and spleen. The stimulatory effect of IFN‐γ upon the pineal gland depends on STAT1/NF‐κB interaction, but the mechanisms controlling IL‐10 effects on melatonin synthesis remain unclear. Here, we evaluated the role of STAT3 and NF‐κB activation by IL‐10 upon the melatonin synthesis of rats' pineal gland, BM, spleen, and peritoneal cells. The results show that IL‐10‐induced interaction of (p)STAT3 with specific NF‐κB dimmers leads to different cell effects. IL‐10 increases the pineal's acetylserotonin O‐methyltransferase (ASMT), N ‐acetylserotonin, and melatonin content via nuclear translocation of NF‐κB/STAT3. In BM, the nuclear translocation of STAT3/p65‐NF‐κB complexes increases ASMT expression and melatonin content. Increased pSTAT3/p65‐NF‐κB nuclear translocation in the spleen enhances phosphorylated serotonin N ‐acetyltransferase ((p)SNAT) expression and melatonin content. Conversely, in peritoneal cells, IL‐10 leads to NF‐κB p50/p50 inhibitory dimmer nuclear translocation, decreasing (p)SNAT expression and melatonin content. In conclusion, IL‐10's effects on melatonin production depend on the NF‐κB subunits interacting with (p)STAT3. Thus, variations of IL‐10 levels and downstream pathways during immune responses might be critical regulatory factors adjusting pineal and extra‐pineal synthesis of melatonin.
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