Laboratory of Veterinary Anatomy, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Beijing Milu Ecological Research Center, Beijing, 100076, China.
Cell Tissue Res. 2017 Sep;369(3):555-565. doi: 10.1007/s00441-017-2644-6. Epub 2017 Jun 28.
Previous study has demonstrated that melatonin plays a critical role in monochromatic-light-induced lymphocyte proliferation in response to T cell mitogen concanavalin A (ConA). However, its intracellular mechanism is still unclear. In this study, we investigate the intracellular signal pathways of melatonin receptor-mediated T-lymphocyte proliferation in the spleens of chicks exposed to different light wavelengths. Results showed that green light enhanced T-lymphocyte proliferation by 2.46-6.83% and increased splenic mRNA and protein expressions of melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) by 16.05-40.43% compared with the white, red and blue light groups. However, pinealectomy resulted in a decrease in T-lymphocyte proliferation and melatonin receptor expression with no statistically significant differences between the different light groups. In vitro experiments showed that the Mel1b selective antagonist 4P-PDOT, the Mel1c selective antagonist prazosin and the mitogen-activated protein kinase kinase-1 (MEK-1) inhibitor PD98059 suppressed both melatonin-induced lymphocyte proliferation in response to ConA and melatonin- and ConA-stimulated extracellular signal-regulated kinase 1/2 (ERK1/2) activity but that the Mel1a/Mel1b non-selective antagonist luzindole did not. In addition, pretreatment with forskolin (FSK, the adenylyl cyclase activator), H89 (the PKA inhibitor), U73122 (the PLC inhibitor) or Go6983 (the broad spectrum PKC inhibitor) markedly attenuated melatonin- and ConA-stimulated T-lymphocyte proliferation and ERK1/2 activity. These results demonstrate that melatonin mediates green-light-induced T-lymphocyte proliferation via the Mel1b and Mel1c receptors by triggering crosstalk between the cAMP/PKA and PLC/PKC signal pathways followed by ERK1/2 activation.
先前的研究表明，褪黑素在单波长光照诱导的淋巴细胞增殖中对 T 细胞有丝分裂原伴刀豆球蛋白 A（ConA）起着关键作用。然而，其细胞内机制尚不清楚。在这项研究中，我们研究了不同波长光照下褪黑素受体介导的鸡脾脏 T 淋巴细胞增殖的细胞内信号通路。结果表明，与白光、红光和蓝光组相比，绿光使 T 淋巴细胞增殖提高了 2.46-6.83%，并使褪黑素受体亚型（Mel1a、Mel1b 和 Mel1c）的脾脏 mRNA 和蛋白表达增加了 16.05-40.43%。然而，松果腺切除术导致 T 淋巴细胞增殖和褪黑素受体表达减少，不同光照组之间无统计学差异。体外实验表明，Mel1b 选择性拮抗剂 4P-PDOT、Mel1c 选择性拮抗剂 prazosin 和丝裂原激活蛋白激酶激酶-1（MEK-1）抑制剂 PD98059 抑制了褪黑素诱导的 ConA 反应性淋巴细胞增殖以及褪黑素和 ConA 刺激的细胞外信号调节激酶 1/2（ERK1/2）活性，但 Mel1a/Mel1b 非选择性拮抗剂 luzindole 没有。此外，预先用 forskolin（FSK，腺苷酸环化酶激活剂）、H89（PKA 抑制剂）、U73122（PLC 抑制剂）或 Go6983（广谱 PKC 抑制剂）预处理明显减弱了褪黑素和 ConA 刺激的 T 淋巴细胞增殖和 ERK1/2 活性。这些结果表明，褪黑素通过触发 cAMP/PKA 和 PLC/PKC 信号通路之间的串扰，然后激活 ERK1/2，介导绿光诱导的 T 淋巴细胞增殖，该通路涉及 Mel1b 和 Mel1c 受体。
