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A Green and Blue Monochromatic Light Combination Therapy Reduces Oxidative Stress and Enhances B-Lymphocyte Proliferation through Promoting Melatonin Secretion

ABSTRACT: Artificial illumination may interfere with biological rhythms and distort physiological homeostasis in avian. Our previous study demonstrated that 660 nm red light exacerbates oxidative stress, but a combination of green and blue lights (G→B) can improve the antibody titer in chickens compared with single monochromatic light. Melatonin acts as an antioxidant which is a critical signaling to the coordination between external light stimulation and the cellular response from the body. This study further clarifies the potential role of melatonin in monochromatic light combination-induced bursa B-lymphocyte proliferation in chickens. A total of 192 chicks were exposed to a single monochromatic light (red (R), green (G), blue (B), or white (W) lights) or various monochromatic light combinations (B→G, G→B, and R→B) from P0 to P42. We used qRT-PCR, MTT, western blotting, immunohistochemistry, and Elisa to explore the effect of a combination of monochromatic light on bursa B-lymphocytes and its intracellular signal pathways. With consistency in the upregulation in melatonin level of plasma and antioxidant enzyme ability, we observed increases in organ index, follicle area, lymphocyte density, B-lymphocyte proliferation, PCNA-positive cells, and cyclin D1 expression in bursa of the G→B group compared with other light-treated groups. Melatonin bound to Mel1a and Mel1c and upregulated p-AKT, p-PKC, and p-ERK expression, thereby activating PI3K/AKT and PKC/ERK signaling and inducing B-lymphocyte proliferation. Overall, these findings suggested that melatonin modulates a combination of green and blue light-induced B-lymphocyte proliferation in chickens by reducing oxidative stress and activating the Mel1a/PI3K/AKT and Mel1c/PKC/ERK pathways.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC8004379 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Previous studies found that melatonin modulates a combination of green-and-blue-light-induced B-lymphocyte proliferation via its membrane receptors Mel1a and Mel1c. However, in addition to its membrane-bound receptors, melatonin also functions through binding to nuclear receptors RORα/RORβ/RORγ. In this study, we raised 120 chicks under 400-700 nm white (WW), 660 nm red (RR), 560 nm green (GG) and 480 nm blue light (BB) from P0 to P26. From P27 to P42, half of the chickens in green, blue and red were switched to blue (G→B), green (B→G) and red (R→B), respectively. We used immunohistochemistry, Western blotting, qRT-PCR, Elisa and MTT to investigate the influence of various monochromatic light combinations on the bursal B lymphocyte apoptosis and oxidative stress levels as well as estimate whether melatonin and its nuclear receptors were involved in this process. Consistent with the increase in the plasma melatonin concentration and antioxidant enzyme activity, we observed that G→B significantly decreased the RORα, RORγ mRNA level, inhibited Bax, Caspase-3 and p-iκb, p-p65 protein expression, increased the IL-10 level and Nrf2, HO-1 protein expression, down-regulated the MDA and pro-inflammatory IL-6, TNF-α and IFN-γ levels in the bursa compared with WW, RR, GG, BB and R→B, respectively. Our in vitro results showed exogenous melatonin supplementation inhibited B-lymphocyte apoptosis, decreased IL-6, TNF-α, IFN-γ and ROS production, down-regulated RORα, RORγ mRNA level and p-iκb and p-p65 protein expression, whereas it improved the IL-10 level and Nrf2 and the HO-1 protein expression in bursal B lymphocyte. Moreover, these responses were abrogated by RORα agonist SR1078 but were mimicked by RORα antagonist SR3335 or RORγ antagonist GSK2981278. In addition, p65 antagonist BAY reversed RORα/RORγ-mediated G→B-inhibited bursal B lymphocyte apoptosis. Overall, we concluded that melatonin nuclear RORα/RORγ mediates G→B-inhibited bursal B lymphocyte apoptosis via reducing oxidative stress and Nfκb expression.

Project description:Many nonvisual functions are regulated by light through a photoreceptive system involving melanopsin-expressing retinal ganglion cells that are maximally sensitive to blue light. Several studies have suggested that the ability of light to modulate circadian entrainment and to induce acute effects on melatonin secretion, subjective alertness, and gene expression decreases during aging, particularly for blue light. This could contribute to the documented changes in sleep and circadian regulatory processes with aging. However, age-related modification in the impact of light on steady-state pupil constriction, which regulates the amount of light reaching the retina, is not demonstrated. We measured pupil size in 16 young (22.8±4 years) and 14 older (61±4.4 years) healthy subjects during 45-second exposures to blue (480 nm) and green (550 nm) monochromatic lights at low (7×10(12) photons/cm2/s), medium (3×10(13) photons/cm2/s), and high (10(14) photons/cm2/s) irradiance levels. Results showed that young subjects had consistently larger pupils than older subjects for dark adaptation and during all light exposures. Steady-state pupil constriction was greater under blue than green light exposure in both age groups and increased with increasing irradiance. Surprisingly, when expressed in relation to baseline pupil size, no significant age-related differences were observed in pupil constriction. The observed reduction in pupil size in older individuals, both in darkness and during light exposure, may reduce retinal illumination and consequently affect nonvisual responses to light. The absence of a significant difference between age groups for relative steady-state pupil constriction suggests that other factors such as tonic, sympathetic control of pupil dilation, rather than light sensitivity per se, account for the observed age difference in pupil size regulation. Compared to other nonvisual functions, the light sensitivity of steady-state pupil constriction appears to remain relatively intact and is not profoundly altered by age.

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A Green and Blue Monochromatic Light Combination Therapy Reduces Oxidative Stress and Enhances B-Lymphocyte Proliferation through Promoting Melatonin Secretion

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