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

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.

Melatonin mediates monochromatic light–induced proliferation of T/B lymphocytes in the spleen via the membrane receptor or nuclear receptor

“…The immunohistochemical results showed the expression levels of 3 NR and their locations in the spleens of the broilers. In addition, the expression levels of the 3 melatonin membrane receptors were determined in the spleen ( Guo et al., 2015 ) (data not shown). In the structure of spleen, the white pulp is composed of many lymphocytes, macrophages, dendritic cells and so on, and it is the center of immune activity, whereas the red pulp contains splenic cords and venous sinuses, including red blood cells, reticular fibers, reticular cells, macrophages, and lymphocytes.…”

“…However, there are few studies about the light color affecting lymphocyte proliferation. Our previous research found that green light ( GL ) promotes the proliferation of T lymphocytes in the thymus ( Chen et al., 2016 ) or in the spleen ( Guo et al., 2017 ), and it can also promote the proliferation of B lymphocytes in the bursa of Fabricius ( Li et al., 2015 ) of chicks.…”

“…Pinealectomy and melatonin administration were used to detect the function of melatonin. The pinealectomy decreased the plasma melatonin levels ( Jin et al., 2011 ) and inhibited monochromatic GL–induced lymphocyte proliferation in the thymus ( Chen et al., 2016 ), spleen ( Guo et al., 2017 ), and bursa of Fabricius ( Li et al., 2015 ) of chicks. In contrast, the addition of melatonin promoted the short-day–induced proliferation of splenocytes when compared with long day in hamsters ( Vishwas and Haldar, 2013 ).…”

Melatonin Receptor Mel1b‐ and Mel1c‐mediated Green Light Induced the Secretion of Growth Hormone in Anterior Pituitary of Chicks

“…For example, melatonin inhibited GnRH secretion by Mel1c in the chick hypothalamus . Melatonin mediated the proliferation of T lymphocytes in GL by Mel1b and Mel1c in the chick spleen . In addition, the roles of the three membrane receptors in the same tissue and organ were different.…”

Udział szlaku sygnałowego cAMP/PKA w hamującym wpływie melatoniny na wydzielanie oksytocyny i wazopresyny z układu podwzgórze–część nerwowa przysadki szczura

“…As mentioned above, H-89 inhibits the activity of several protein kinases and has various non-PKA-based effects. In addition, melatonin is known to act by modulating signal transduction cascades mediated by various kinases other than PKA, such as MAPK, ERK1/2, and PKC [42][43][44][45]. Melatonin, acting via the MT 1 receptor, and the cAMP-mediated pathways may also elicit signalling responses involving the regulation of chloride, sodium, potassium, or calcium fluxes and of specific ion channels, such as cAMP-mediated phosphorylation of calcium-activated potassium channels (BK Ca ), voltage-dependent calcium channels (VDCC), or inward-rectifier potassium channels (Kir), depending on the cell type [2,46].…”