Physiological crosstalk between the AC/PKA and PLC/PKC pathways modulates melatonin-mediated, monochromatic-light-induced proliferation of T-lymphocytes in chickens
Physiological crosstalk between the AC/PKA and PLC/PKC pathways modulates melatonin-mediated, monochromatic-light-induced proliferation of T-lymphocytes in chickens
复制标题
AC/PKA 和 PLC/PKC 通路之间的生理串扰调节褪黑激素介导的、单色光诱导的鸡 T 淋巴细胞增殖
DOI：
10.1007/s00441-017-2644-6
复制
发表时间：
2017-09-01
影响因子：
3.6
通讯作者：
Chen, Yaoxing
中科院分区：
文献类型：
--
作者：
Guo, Qingyun;Wang, Zixu;Chen, Yaoxing
先前的研究表明，褪黑激素在单色光诱导的淋巴细胞增殖中对T细胞有丝分裂原conanalin a （ConA）起关键作用。然而，其细胞内机制尚不清楚。在本研究中，我们研究了褪黑素受体介导的t淋巴细胞在暴露于不同波长光下的雏鸡脾脏中的细胞内信号通路。结果显示，与白光、红光和蓝光组相比，绿光可使小鼠t淋巴细胞增殖增强2.46 ~ 6.83%，脾脏褪黑素受体（Mel1a、Mel1b和Mel1c） mRNA和蛋白表达增加16.05 ~ 40.43%。然而，松果体切除术导致t淋巴细胞增殖和褪黑激素受体表达减少，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和丝裂原活化蛋白激酶激酶1 （MEK-1）抑制剂PD98059抑制褪黑素诱导的ConA和褪黑素刺激的细胞外信号调节激酶1/2 （ERK1/2）活性，而Mel1a/Mel1b非选择性拮抗剂luzindole则没有这种作用。此外，用福斯克林（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）预处理可显著减弱褪黑素和cona刺激的t淋巴细胞增殖和ERK1/2活性。这些结果表明，褪黑激素通过Mel1b和Mel1c受体介导绿光诱导的t淋巴细胞增殖，触发cAMP/PKA和PLC/PKC信号通路之间的串扰，随后激活ERK1/2。
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.