Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model

Qin, Bing; Yun-long, Deng

doi:10.1016/j.imlet.2014.11.014

Cited by 39 publications

(35 citation statements)

References 55 publications

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“…As in murine inflammatory arthritis, cryptochrome appears to have an anti-inflammatory role in murine atherosclerosis, with reduced expression of TLR2 and -4 in murine CRY1-overexpression models. There is also reduced expression of the adhesion molecules VCAM-1, ICAM-1, and E-selectin and reduced serum levels of proinflammatory cytokines, including TNFa, IL-1a, and IL-6 [107,108]. NF-kB activation is also regulated by cryptochrome in this model, with attenuated NF-kB activation in CRY1 overexpression in vascular endothelial cells stimulated with endotoxin or TNFa [107].…”

Section: Atherosclerosismentioning

confidence: 69%

A matter of time: study of circadian clocks and their role in inflammation

Carter

Durrington²,

Gibbs³

et al. 2016

Journal of Leukocyte Biology

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Circadian rhythms regulate changes in physiology, allowing organisms to respond to predictable environmental demands varying over a 24 h period. A growing body of evidence supports a key role for the circadian clock in the regulation of immune functions and inflammatory responses, which influence the understanding of infections and inflammatory diseases and their treatment. A variety of experimental methods have been used to assess the complex bidirectional crosstalk between the circadian clock and inflammation. In this review, we summarize the organization of the molecular clock, experimental methods used to study circadian rhythms, and both the inflammatory and immune consequences of circadian disturbance.

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Section: Atherosclerosismentioning

confidence: 69%

A matter of time: study of circadian clocks and their role in inflammation

Carter

Durrington²,

Gibbs³

et al. 2016

Journal of Leukocyte Biology

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“…Taken together, our observations suggest that the repressive arm of the molecular clock, and specifically CRY, contributes to the reduction in inflammation observed during the night. Both CRY ( 41 – 44 ) and PER ( 45 – 48 ) have been implicated in regulation of inflammatory processes. However, although FLSs derived from mice lacking cry1/2 demonstrated a proinflammatory phenotype, FLSs derived from per2 −/− mice did not show an increased response to TNFα stimulation.…”

Section: Discussionmentioning

confidence: 99%

The circadian clock regulates inflammatory arthritis

et al. 2016

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There is strong diurnal variation in the symptoms and severity of chronic inflammatory diseases, such as rheumatoid arthritis. In addition, disruption of the circadian clock is an aggravating factor associated with a range of human inflammatory diseases. To investigate mechanistic links between the biological clock and pathways underlying inflammatory arthritis, mice were administered collagen (or saline as a control) to induce arthritis. The treatment provoked an inflammatory response within the limbs, which showed robust daily variation in paw swelling and inflammatory cytokine expression. Inflammatory markers were significantly repressed during the dark phase. Further work demonstrated an active molecular clock within the inflamed limbs and highlighted the resident inflammatory cells, fibroblast-like synoviocytes (FLSs), as a potential source of the rhythmic inflammatory signal. Exposure of mice to constant light disrupted the clock in peripheral tissues, causing loss of the nighttime repression of local inflammation. Finally, the results show that the core clock proteins cryptochrome (CRY) 1 and 2 repressed inflammation within the FLSs, and provide novel evidence that a CRY activator has anti-inflammatory properties in human cells. We conclude that under chronic inflammatory conditions, the clock actively represses inflammatory pathways during the dark phase. This interaction has exciting potential as a therapeutic avenue for treatment of inflammatory disease.—Hand, L. E., Hopwood, T. W., Dickson, S. H., Walker, A. L., Loudon, A. S. I., Ray, D. W., Bechtold, D. A., Gibbs, J. E. The circadian clock regulates inflammatory arthritis.

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“…Abnormal regulation of circadian clocks in peripheral tissues is suggested to cause cell dysfunction and chronic diseases (8,30). It has been shown that the clock machinery including nuclear receptors controls inflammatory immune responses (5,17,19,(23)(24)(25)(31)(32)(33). We found that the level and expression of clock proteins (BMAL1 and PER2) and associated nuclear receptors (REV-ERBa) were reduced in PBMCs and sputum cells (mainly inflammatory cells [i.e., macrophages and neutrophils]) and in lungs from smokers and patients with COPD.…”

Section: Original Researchmentioning

confidence: 99%

Disruption of Sirtuin 1–Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease

Yao¹,

Sundar²,

Huang³

et al. 2015

Am J Respir Cell Mol Biol

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Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death, and it is characterized by abnormal inflammation and lung function decline. Although the circadian molecular clock regulates inflammatory responses, there is no information available regarding the impact of COPD on lung molecular clock function and its regulation by sirtuin 1 (SIRT1). We hypothesize that the molecular clock in the lungs is disrupted, leading to increased inflammatory responses in smokers and patients with COPD and its regulation by SIRT1. Lung tissues, peripheral blood mononuclear cells (PBMCs), and sputum cells were obtained from nonsmokers, smokers, and patients with COPD for measurement of core molecular clock proteins (BMAL1, CLOCK, PER1, PER2, and CRY1), clock-associated nuclear receptors (REV-ERBa, REV-ERBb, and RORa), and SIRT1 by immunohistochemistry, immunofluorescence, and immunoblot. PBMCs were treated with the SIRT1 activator SRT1720 followed by LPS treatment, and supernatant was collected at 6-hour intervals. Levels of IL-8, IL-6, and TNF-a released from PBMCs were determined by ELISA. Expression of BMAL1, PER2, CRY1, and REV-ERBa was reduced in PBMCs, sputum cells, and lung tissues from smokers and patients with COPD when compared with nonsmokers. SRT1720 treatment attenuated LPS-mediated reduction of BMAL1 and REV-ERBa in PBMCs from nonsmokers. Additionally, LPS differentially affected the timing and amplitude of cytokine (IL-8, IL-6, and TNF-a) release from PBMCs in nonsmokers, smokers, and patients with COPD. Moreover, SRT1720 was able to inhibit LPS-induced cytokine release from cultured PBMCs. In conclusion, disruption of the molecular clock due to SIRT1 reduction contributes to abnormal inflammatory response in smokers and patients with COPD.Keywords: circadian rhythm; SIRT1; REV-ERBa; BMAL1; smokers Clinical RelevanceAlthough the circadian clock regulates the inflammatory response, there is no information available regarding the impact of chronic obstructive pulmonary disease (COPD) on molecular clock function in peripheral tissues and its modulation by sirtuin 1 (SIRT1). We report here that clock proteins, including BMAL1 and REV-ERBa, are reduced in peripheral tissues from patients with COPD in part owing to SIRT1 reduction. LPS differently affects the timing and amplitude of cytokine release from peripheral blood mononuclear cells among nonsmokers, smokers, and patients with COPD. The SIRT1 activator SRT1720 is able to inhibit LPS-induced cytokine release in peripheral blood mononuclear cells. This has implications in the pathogenesis and pharmacological chronotherapy of COPD.

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Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model

Cited by 39 publications

References 55 publications

A matter of time: study of circadian clocks and their role in inflammation

A matter of time: study of circadian clocks and their role in inflammation

The circadian clock regulates inflammatory arthritis

Disruption of Sirtuin 1–Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease

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