Persistent T lymphocyte rhythms despite suppressed circadian clock outputs in rats

Deprés-Brummer, Petra; Bourin, Philippe; Pagès, Nicole; Metzger, Gérard; Lévi, Françis

doi:10.1152/ajpregu.1997.273.6.r1891

Cited by 39 publications

(35 citation statements)

References 23 publications

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“…These findings indicate the ability of peripheral circadian oscillators to remain synchronized in the absence of the established central pacemaker. In a separate investigation, we found that lymphocyte subset rhythms persisted in rats with suppressed rest-activity and body temperature rhythms as a result of prolonged exposure to constant light (15).…”

Section: Discussionmentioning

confidence: 80%

Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Filipski

King²,

Etienne³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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. Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice. Am J Physiol Regul Integr Comp Physiol 287: R844 -R851, 2004. First published June 24, 2004 10.1152/ajpregu. 00085.2004.-Rest-activity or cortisol rhythms can be altered in cancer patients, a condition that may impair the benefits from a timed delivery of anticancer treatments. In rodents, the circadian pattern in rest-activity is suppressed by the destruction of the suprachiasmatic nuclei (SCN) in the hypothalamus. We sought whether such ablation would result in a similar alteration of cellular rhythms known to be relevant for anticancer drug chronopharmacology. The SCN of 77 B6D2F1 mice synchronized with 12 h of light and 12 h of darkness were destroyed by electrocoagulation [SCN(Ϫ)], while 34 animals were sham operated. Activity and body temperature were recorded by telemetry. Blood and organs were sampled at one of six circadian times for determinations of serum corticosterone concentration, blood leukocyte count, reduced glutathione (GSH), and dihydropyrimidine dehydrogenase (DPD) mRNA expression in liver and cell cycle phase distribution of bone marrow cells. Sham-operated mice displayed significant 24-h rhythms in rest-activity and body temperature, whereas such rhythms were found in none and in 15% of the SCN(Ϫ) mice, respectively. SCN lesions markedly altered the rhythmic patterns in serum corticosterone and liver GSH, which became nonsinusoidal. Liver DPD mRNA expression and bone marrow cell cycle phase distribution displayed similar 24-h sinusoidal patterns in shamoperated and SCN(Ϫ) mice. These results support the existence of another light-dark entrainable pacemaker that can coordinate cellular functions in peripheral organs. They suggest that the delivery of anticancer treatments at an optimal time of day may still be beneficial, despite suppressed rest-activity or cortisol rhythms. circadian coordination; cancer chronotherapeutics; cortisol; cell cycle; dihydropyrimidine dehydrogenase APPROXIMATELY 25% of cancer patients displayed profound alterations of rest-activity pattern and cortisol rhythm independently of tumor stage or general condition (32-34). Poorer tumor response and shorter survival were reported in these patients compared with those with near normal circadian function (36,43). Such altered circadian function could also impair the therapeutic benefit that can result from chronotherapeutics, i.e., the delivery of anticancer treatments at selected times of day (12,23,26,27).This treatment optimization method is based on the regulation of cellular metabolism and proliferation by a molecular clock. This clock consists of interconnected molecular loops involving up to 12 specific clock genes. It has been uncovered in most mammalian tissues (21,35,41,42) and rhythmically regulates the transcription of 5-10% of the genome (14,21,41,42). Indeed, sustained rhythms in transcription or other cellular functions have been demonstrated in cultured mammalian cells, giving rise to the con...

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Section: Discussionmentioning

confidence: 80%

Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Filipski

King²,

Etienne³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

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“…In this sense, it is yet to be deciphered whether the SCN, the central circadian pacemaker, is involved in the entrainment of NK cell function, as well as the coordinating signals by which circadian information may be conveyed to NK cells and other lymphocytes. Rhythms in the number of circulating T cells persisted in rats with disrupted circadian outputs (51). Similarly, SCN ablation did not affect the 24-h rhythms in cell cycle phase distribution in bone marrow cells (52), suggesting that some rhythms in the immune system may be SCNindependent.…”

Section: Discussionmentioning

confidence: 95%

Circadian Oscillations of Clock Genes, Cytolytic Factors, and Cytokines in Rat NK Cells

Arjona

Sarkar

2005

The Journal of Immunology

192

141

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A growing body of knowledge is revealing the critical role of circadian physiology in the development of specific pathological entities such as cancer. NK cell function participates in the immune response against infection and malignancy. We have reported previously the existence of a physiological circadian rhythm of NK cell cytolytic activity in rats, suggesting the existence of circadian mechanisms subjacent to NK cell function. At the cellular level, circadian rhythms are originated by the sustained transcriptional-translational oscillation of clock genes that form the cellular clock apparatus. Our aim in this study was to investigate the presence of molecular clock mechanisms in NK cells as well as the circadian expression of critical factors involved in NK cell function. For that purpose, we measured the circadian changes in the expression of clock genes (Per1, Per2, Bmal1, Clock), Dbp (a clock-controlled output gene), CREB (involved in clock signaling), cytolytic factors (granzyme B and perforin), and cytokines (IFN-γ and TNF-α) in NK cells enriched from the rat spleen. The results obtained from this study demonstrate for the first time the existence of functional molecular clock mechanisms in NK cells. Moreover, the circadian expression of cytolytic factors and cytokines in NK cells reported in this study emphasizes the circadian nature of NK cell function.

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“…In addition, circadian variations in cortisol plasma levels have been strongly associated with circadian variations of the immune system especially NK function (44). However, Depres-Brummer et al (45), showed persistent rhythms in T lymphocyte blood counts in rats deprived of circadian clock outputs such as catecholamines. Further research is needed to identify the role of neuroendocrine hormones in mediating the influence of the central clock on NK rhythm.…”

Section: Discussionmentioning

confidence: 99%

Circadian Rhythms of Granzyme B, Perforin, IFN-γ, and NK Cell Cytolytic Activity in the Spleen: Effects of Chronic Ethanol

Arjona

Boyadjieva

Sarkar

2004

The Journal of Immunology

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Recent studies show that alterations in the body’s biological rhythms can lead to serious pathologies, including cancer. Acute and chronic ethanol consumption impairs the immune system by causing specific defects in the cellular components of the innate immune response and by creating increased risk and susceptibility to infections and cancer. NK cells are critical for immune surveillance against infected and malignant cells. To assess whether NK cell function follows a circadian trend and to determine ethanol effects on this rhythm, we measured, over a 24-h period, mRNA and protein levels of granzyme B, perforin, and the cytokine IFN-γ, as well as NK cell activity, in the splenocytes of ad libitum-fed, pair-fed, and ethanol-fed Sprague Dawley male rats. Circadian rhythms were found in mRNA and protein levels of granzyme B, perforin, and IFN-γ. A circadian pattern was also detected in NK cell cytolytic activity. Our data further demonstrated how chronic ethanol suppressed NK cell activity by directly disrupting the circadian rhythms of granzyme B, perforin, and IFN-γ. These findings identify the circadian functions of splenic NK cells and show the vulnerability of these rhythms to chronic ethanol.

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Persistent T lymphocyte rhythms despite suppressed circadian clock outputs in rats

Cited by 39 publications

References 23 publications

Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Circadian Oscillations of Clock Genes, Cytolytic Factors, and Cytokines in Rat NK Cells

Circadian Rhythms of Granzyme B, Perforin, IFN-γ, and NK Cell Cytolytic Activity in the Spleen: Effects of Chronic Ethanol

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