Laboratory of Chronopharmacology, Institute of Bioscience, University of São Paulo, São Paulo, SP, Brazil.
J Pineal Res. 2013 Oct;55(3):240-6. doi: 10.1111/jpi.12066. Epub 2013 Jun 10.
Many cells in the organism besides pinealocytes, synthesize melatonin. Here, we evaluate both the mechanism of zymosan-induced melatonin synthesis and its autocrine effect in human colostral mononuclear cells. The synthesis of melatonin was induced by activation of the transcription factor nuclear factor kappa B (NF-κB), as either the blockade of the proteasome or the binding of NF-κB to DNA inhibits zymosan-induced melatonin synthesis. As observed in RAW 264.7 lineage cells, the dimer involved is RelA/c-Rel. Melatonin plays a direct role in mononuclear cell activity, increasing zymosan-induced phagocytosis by stimulating MT2 melatonin receptors and increasing the expression of dectin-1. This role was confirmed by the blockade of melatonin receptors using the competitive antagonist luzindole and the MT2 -selective partial agonist 4P-PDOT. In summary, we show that melatonin produced by immune-competent cells acts in an autocrine manner, enhancing the clearance of pathogens by increasing phagocyte efficiency. Given that these cells are present in human colostrum for 4 or 5 days after birth, this mechanism may be relevant for the protection of infant health.
除松果体细胞外，机体内还有许多细胞能够合成褪黑素。在这里，我们评估了真菌聚糖诱导褪黑素合成的机制及其在人初乳单核细胞中的自分泌作用。褪黑素的合成是通过转录因子核因子 κB（NF-κB）的激活诱导的，因为蛋白酶体的阻断或 NF-κB 与 DNA 的结合抑制真菌聚糖诱导的褪黑素合成。正如在 RAW 264.7 细胞系中观察到的那样，涉及的二聚体是 RelA/c-Rel。褪黑素通过刺激 MT2 褪黑素受体和增加 dectin-1 的表达，直接作用于单核细胞活性，增加真菌聚糖诱导的吞噬作用。这一作用通过使用竞争性拮抗剂 luzindole 和 MT2 选择性部分激动剂 4P-PDOT 阻断褪黑素受体得到了证实。总之，我们表明，免疫活性细胞产生的褪黑素以自分泌的方式发挥作用，通过提高吞噬细胞的效率来增强清除病原体的能力。鉴于这些细胞在出生后 4 或 5 天存在于人初乳中，这种机制可能与保护婴儿健康有关。
