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Physiological crosstalk between the AC/PKA and PLC/PKC pathways modulates melatonin-mediated, monochromatic-light-induced proliferation of T-lymphocytes in chickens

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Abstract

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.

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Acknowledgements

This work was supported by the National High Technology Research and Development Program of China (2013AA102306), Chinese National Nature of Science Foundation (31172277, 31272516, 31372387, 31472157 and 31672501), and Chinese Specialized Research Fund for the Doctoral Program of Higher Education (20130008110031).

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  1. Laboratory of Veterinary Anatomy, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China

    Qingyun Guo, Zixu Wang, Yulan Dong, Jing Cao & Yaoxing Chen

  2. Beijing Milu Ecological Research Center, Beijing, 100076, China

    Qingyun Guo

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  1. Qingyun Guo
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Correspondence to Yaoxing Chen.

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Guo, Q., Wang, Z., Dong, Y. et al. Physiological crosstalk between the AC/PKA and PLC/PKC pathways modulates melatonin-mediated, monochromatic-light-induced proliferation of T-lymphocytes in chickens. Cell Tissue Res 369, 555–565 (2017). https://doi.org/10.1007/s00441-017-2644-6

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