Abstract
Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU10/spleen) while the activity of a single NK cell (LU10/106 cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of carnosine on restraint-evoked immunocompromise might be via carnosine-histamine metabolic pathway. Taken together, carnosine maintained spleen lymphocyte number by inhibiting lymphocyte apoptosis and stimulating lymphocyte proliferation, thus prevented immunocompromise in restraint-stressed mice.
Highlights
Carnosine (b-alanyl-L-histidine), a naturally occurring dipeptide, is mainly distributed in the brain, muscles, and other innervated tissues [1,2]
We evaluated the effects of carnosine on Natural Killer (NK) cell number and cytotoxic activity in spleen by flow cytometry
Our research found that restraint stress markedly reduced spleen lymphocyte number and caused spleen atrophy
Summary
Carnosine (b-alanyl-L-histidine), a naturally occurring dipeptide, is mainly distributed in the brain, muscles, and other innervated tissues [1,2]. Earlier reports indicated that carnosine supplementation could regulate immune function, such as extending the lifespan of human CD4+ T cells [11], modulating immune response of rabbits against Schistosoma mansoni antigens and regulating the functions of neutrophils [12,13]. Underlying mechanism of these effects was suggested to be related with the antioxidative property of carnosine [14]. Recent studies found that carnosine could exert anti-stress effects through histamine metabolic pathway [15]. Earlier studies indicated that histamine plays an important role in the alleviation of stress-caused adverse effects [17]
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