A circadian based inflammatory response – implications for respiratory disease and treatment

Comas, Maria; Gordon, Christopher J.; Oliver, Brian G.; Stow, Nicholas W.; King, Gregory G.; Sharma, Pawan; Ammit, Alaina J.; Grunstein, Ronald R.; Phillips, Craig L.

doi:10.1186/s41606-017-0019-2

Cited by 45 publications

(34 citation statements)

References 264 publications

(302 reference statements)

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“…5 The proteins A20 ( TNFAIP3 ) and IκBα ( NFKBIA ) are part of the two main negative feedback loops of NF-κB-driven transcription. 5 Furthermore, TNFα is a potent inducer of IL-8 secretion, through a transcriptional mechanism regulated by NF-κB. Increases in IL-8 and TNFα have been identified in several cytokine and immune ME/CFS studies.…”

Section: Resultsmentioning

confidence: 99%

“…The three top upregulated genes in our study, IL8, NFKBIA and TNFAIP3 , are early responders to TNF-induced NF-κB activation. 5 The proteins A20 ( TNFAIP3 ) and IκBα ( NFKBIA ) are part of the two main negative feedback loops of NF-κB-driven transcription. 5 Furthermore, TNFα is a potent inducer of IL-8 secretion, through a transcriptional mechanism regulated by NF-κB.…”

Section: Resultsmentioning

confidence: 99%

“…The three top upregulated genes in our study, IL8, NFKBIA and TNFAIP3, are early responders to TNF-induced NF-κB activation. 5 The proteins A20 (TNFAIP3) and IκBα (NFKBIA) are part of the two Table 1. Transcripts with altered gene expression in the ME/CFS group compared to healthy controls (P < 0.01).…”

Section: Anti-inflammatory Responders To Tnfα and Nf-κbmentioning

confidence: 99%

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Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome

Sweetman

Ryan

Edgar

et al. 2019

Int J Immunopathol Pharmacol

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood disease affecting 0.2%–2% of the global population. To gain insight into the pathophysiology of ME/CFS in New Zealand, we examined the transcriptomes of peripheral blood mononuclear cells by RNA-seq analysis in a small well-characterized patient group (10 patients), with age/gender-matched healthy controls (10 control subjects). Twenty-seven gene transcripts were increased 1.5- to sixfold and six decreased three- to sixfold in the patient group (P < 0.01). The top enhanced gene transcripts, IL8, NFΚBIA and TNFAIP3, are functionally related to inflammation, and significant changes were validated for IL8 and NFΚBIA by quantitative polymerase chain reaction (qPCR). Functional network analysis of the altered gene transcripts (P < 0.01) detected interactions between the products related to inflammation, circadian clock function, metabolic dysregulation, cellular stress responses and mitochondrial function. Ingenuity pathway analysis (P < 0.05) provided further insights into the dysfunctional physiology, highlighting stress and inflammation pathways. This analysis provides novel insights into the molecular changes in ME/CFS and contributes to the understanding of the pathophysiological mechanisms of the disease.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome

Sweetman

Ryan

Edgar

et al. 2019

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

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“…Orthotopic xenografts are largely absent in BMAL1 manipulation studies and should be considered for their greater clinical relevance in BMAL1 and other clock gene studies. Alternatively, as the clock is tied to inflammation and immunity, the use of humanised mouse models or simply immunocompetent mouse models may unearth new pathways by which abrogation of the molecular clock impacts tumourigenesis (Comas et al, 2017).…”

Section: Bmal1mentioning

confidence: 99%

Cancer clocks in tumourigenesis: the p53 pathway and beyond

Stephenson

Usselmann

Tergaonkar

et al. 2021

Endocrine-Related Cancer

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Circadian rhythms regulate a vast array of physiological and cellular processes, as well as the hormonal milieu, to keep our cells synchronised to the light-dark cycle. Epidemiologic studies have implicated circadian disruption in the development of breast and other cancers, and numerous clock genes are dysregulated in human tumours. Here we review the evidence that circadian rhythms, when altered at the molecular level, influence cancer growth. We also note some common pitfalls in circadian-cancer research and how they might be avoided to maximise comparable results and minimise misleading data. Studies of circadian gene mutant mice, and human cancer models in vitro and in vivo, demonstrate that clock genes can impact tumourigenesis. Clock genes influence important cancer related pathways, ranging from p53-mediated apoptosis to cell cycle progression. Confusingly, clock dysfunction can be both pro- or anti- tumourigenic in a model and cell type specific manner. Due to this duality, there is no canonical mechanism for clock interaction with tumourigenic pathways. To understand the role of the circadian clock in patients’ tumours requires analysis of the molecular clock status compared to healthy tissue. Novel mathematical approaches are under development, but this remains largely aspirational, and is hampered by a lack of temporal information in publicly available datasets. Current evidence broadly supports the notion that the circadian clock is important for cancer biology. More work is necessary to develop an overarching model of this connection. Future studies would do well to analyse the clock network in addition to alterations in single clock genes.

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“…Although many factors have been identified that may contribute to the industrialized microbiota (Sonnenburg and Sonnenburg, 2019), chronic low-grade inflammation (Rohleder, 2014), and vulnerability to exaggerated or prolonged inflammatory responses to psychosocial stress (Böbel et al, 2018), one common factor associated with the modern lifestyle is circadian disruption. Circadian disruption alters the microbiome (Voigt et al, 2014(Voigt et al, , 2016Deaver et al, 2018;Wu et al, 2018;Parkar et al, 2019), induces chronic low-grade inflammation (Li et al, 2018;Inokawa et al, 2020), and induces exaggerated inflammatory responses to immune challenge (Castanon-Cervantes et al, 2010;Adams et al, 2013;Brager et al, 2013;Guerrero-Vargas et al, 2015;Comas et al, 2017). Circadian disruption, in turn, increases risk of stress-related psychiatric disorders (Karatsoreos, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a “Two Hit” Stressor Model

et al. 2021

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Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a “two hit” stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day –28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days –21, –14, –7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0–56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days –1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.

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A circadian based inflammatory response – implications for respiratory disease and treatment

Cited by 45 publications

References 264 publications

Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome

Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome

Cancer clocks in tumourigenesis: the p53 pathway and beyond

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a “Two Hit” Stressor Model

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