Effect of Melatonin Treatment on 24‐h Variations in Responses to Mitogens and Lymphocyte Subset Populations in Rat Submaxillary Lymph Nodes

Castrillón, Patricia O.; Esquifino, Ana I.; Varas, Alberto; Zapata, A.; Cutrera, Rodolfo A.; Cardinali, Daniel P.

doi:10.1046/j.1365-2826.2000.00519.x

Cited by 43 publications

(33 citation statements)

References 33 publications

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“…39 for example), which contrasts our data showing constant numbers of T cell subsets and B cells in mouse superficial LNs. Melatonin can alter the balance of T cell subsets (40). Because rats produce a high-amplitude melatonin rhythm (41), whereas C57BL/6 mice produce very low FIGURE 4.…”

Section: Discussionmentioning

confidence: 99%

Circadian Variation of the Response of T Cells to Antigen

Fortier¹,

Rooney²,

Dardente³

et al. 2011

The Journal of Immunology

156

171

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Circadian clocks regulate many important aspects of physiology, and their disturbance leads to various medical conditions. Circadian variations have been found in immune system variables, including daily rhythms in circulating WBC numbers and serum concentration of cytokines. However, control of immune functional responses by the circadian clock has remained relatively unexplored. In this study, we show that mouse lymph nodes exhibit rhythmic clock gene expression. T cells from lymph nodes collected over 24 h show a circadian variation in proliferation after stimulation via the TCR, which is blunted in Clock gene mutant mice. The tyrosine kinase ZAP70, which is just downstream of the TCR in the T cell activation pathway and crucial for T cell function, exhibits rhythmic protein expression. Lastly, mice immunized with OVA peptide-loaded dendritic cells in the day show a stronger specific T cell response than mice immunized at night. These data reveal circadian control of the Ag-specific immune response and a novel regulatory mode of T cell proliferation, and may provide clues for more efficient vaccination strategies.

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Section: Discussionmentioning

confidence: 99%

Circadian Variation of the Response of T Cells to Antigen

Fortier¹,

Rooney²,

Dardente³

et al. 2011

The Journal of Immunology

156

171

View full text Add to dashboard Cite

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“…151 The Th1 cells directly kill tumor cells by releasing cytokines which activate "death receptors" on the tumor cell surface.…”

Section: Melatonin Immunoenhancement As a Part Of Its Oncostatic Effectmentioning

confidence: 99%

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

et al. 2008

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189predisposing factors for the development of cancer in humans.2,3 A recent study involving 44 000 pairs of Scandinavian twins suggested that environmental factors are paramount contributors in cancer development. 4 The human body is well equipped with both immune and nonimmune anticarcinogenic mechanisms for fighting cancer. Natural killer (NK) lymphocytes play an important role in inhibiting tumor growth and metastases. 5 Many studies implicate oxidative stress in precipitating the 3 steps of carcinogenesis, that is, its initiation, promotion, and progression.6 Free radicals and reactive oxygen species (ROS) generated by environmental carcinogens, or by metabolic alterations, cause DNA damage and genetic instability. [6][7][8] DNA damage induced by oxidative stress is the major contributor to the development of malignancy. It is wellknown that natural antioxidant defenses are active in counteracting the production of free radicals and the molecular damage inflicted by them on DNA and other C ancer is a major health problem in industrialized and developing countries. Most diagnoses of cancer occur in people more than 55 years of age, with prostate cancer being the leading type of cancer in males followed by lung cancer. In females, breast and colon cancers are the leading types of cancer. Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep/wake cycle, as well as circadian rhythms generally, melatonin is involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and animal studies have now shown that melatonin also has important oncostatic properties. Both at physiological and pharmacological doses melatonin exerts growth inhibitory effects on breast cancer cell lines. In hepatomas, through its activation of MT 1 and MT 2 receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth of prostate tumors via activation of MT 1 receptors thereby inducing translocation of the androgen receptor to the cytoplasm and inhibition of the effect of endogenous androgens. There is abundant evidence indicating that melatonin is involved in preventing tumor initiation, promotion, and progression. The anticarcinogenic effect of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic properties. Melatonin's oncostatic actions include the direct augmentation of natural killer (NK) cell activity, which increases immunosurveillance, as well as the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12, and interferon (IFN)-γ. In addition to its direct oncostatic action, melatonin protects hematopoietic precursors from the toxic effect of anticancer chemotherapeutic drugs. Melatonin secretion...

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“…Exogenous melatonin, given at the same time of day, can entrain physiological and behavioral rhythms (e.g., body temperature and rest-activity cycles) (Arendt and Skene, 2005). Melatonin has been reported to modulate a myriad of other functions, including visual, neuroendocrine, reproductive, neuroimmune, and vascular physiology (Arendt, 2000;Cagnacci et al, 2000;Castrillón et al, 2000;Monti and Cardinali, 2000;Maestroni, 2001;Sharkey et al, 2009). Because the duration of nocturnal melatonin secretion is directly proportional to the length of the night, this hormone also provides a signal for seasonal change.…”

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confidence: 99%