The RelB subunit of NFκB acts as a negative regulator of circadian gene expression

Bellet, Marina Maria; Zocchi, Loredana; Sassone–Corsi, Paolo

doi:10.4161/cc.21669

Cited by 60 publications

(54 citation statements)

References 50 publications

(44 reference statements)

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“…In our experiments, rhythmicity of circadian and metabolic genes is suppressed or attenuated at the site of infection, supporting the concept of intimate bidirectional communication between the circadian and immune systems (36,37). Our hypothesis is that immune factors contribute to the daily coordination of the circadian system, but powerful immunological challenges send signals to disrupt this regulation, possibly by uncoupling some of the circadian outputs, leading to reduction of the amplitude of the oscillations.…”

Section: Discussionsupporting

confidence: 81%

Circadian clock regulates the host response to Salmonella

Bellet¹,

Deriu

Liu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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224

198

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Organisms adapt to day-night cycles through highly specialized circadian machinery, whose molecular components anticipate and drive changes in organism behavior and metabolism. Although many effectors of the immune system are known to follow daily oscillations, the role of the circadian clock in the immune response to acute infections is not understood. Here we show that the circadian clock modulates the inflammatory response during acute infection with the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). Mice infected with S. Typhimurium were colonized to higher levels and developed a higher proinflammatory response during the early rest period for mice, compared with other times of the day. We also demonstrate that a functional clock is required for optimal S. Typhimurium colonization and maximal induction of several proinflammatory genes. These findings point to a clock-regulated mechanism of activation of the immune response against an enteric pathogen and may suggest potential therapeutic strategies for chronopharmacologic interventions.clock genes | inflammation | gastroenteritis | intestine | microbes

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Section: Discussionsupporting

confidence: 81%

Circadian clock regulates the host response to Salmonella

Bellet¹,

Deriu

Liu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

224

198

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“…CLOCK complexes with p65 causing increased acetylation and phosphorylation of p65 and enhancing the activity of the NF-B complex [115]. Both CLOCK mutant MEFs [116] and bone marrow derived macrophages (BMDMs) lacking CLOCK, are less responsive to LPS, and TNF␣ induced NF-B activation [65]. Therefore CLOCK may drive, whereas BMAL1 may limit, pro-inflammatory responses in macrophages.…”

Section: Clockmentioning

confidence: 99%

“…[66,116] Clock 19 Global • Obese and display impaired glucose sensitivity with insulin resistance and reduced islet size [112,113] • Increased plasma triglyceride and glucose levels [85,114] • Increased fibrotic damage in model of pulmonary fibrosis [87] • Impaired anti-oxidant defense [87] Cry1/Cry2 Global • Increased NAD+ and ATP. Decreased lactate and triglycerides in MEFs [95] • Greater inflammatory damage in CIA model [146] • Increased Cxcl1.…”

Section: Bmal1-a Master Regulatormentioning

confidence: 99%

Immunometabolism: Is it under the eye of the clock?

Early

Curtis

2016

Seminars in Immunology

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“…Petrzilka and colleagues extended this work and showed that TNF-α requires p38 mitogenactivated protein kinases (MAPK) and/or calcium signalling to upregulate expression of several core clock genes but it can downregulate Dbp (clock controlled gene) expression independently from p38 but requires calcium signalling (Petrzilka et al 2009). And Bellet and co-workers showed that the RelB subunit of NF-kB interacts with BMAL1 protein and represses the circadian expression of Dbp (Bellet et al 2012). Overall, these studies provide clues to understand the cross-talk between the circadian and immune systems in inflammatory diseases.…”

Section: There Is a Circadian Variation In Immune Functionmentioning

confidence: 97%

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

Comas

Gordon

Oliver

et al. 2017

Sleep Science Practice

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Circadian clocks regulate the daily timing of many of our physiological, metabolic and biochemical functions. The immune system also displays circadian oscillations in immune cell count, synthesis and cytokine release, clock gene expression in cells and organs of the immune system as well as clock-controlled genes that regulate immune function. Circadian disruption leads to dysregulation of immune responses and inflammation which can further disrupt circadian rhythms. The response of organisms to immune challenges, such as allergic reactions also vary depending on time of the day, which can lead to detrimental responses particularly during the rest and early active periods. This review evaluates what is currently known in terms of circadian biology of immune response and the cross-talk between circadian and immune system. We discuss the circadian pattern of three respiratory-related inflammatory diseases, chronic obstructive pulmonary disease, allergic rhinitis and asthma. Increasing our knowledge on circadian patterns of immune responses and developing chronotherapeutic studies in inflammatory diseases with strong circadian patterns will lead to preventive measures as well as improved therapies focussing on the circadian rhythms of symptoms and the daily variation of the patients' responses to medication.

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The RelB subunit of NFκB acts as a negative regulator of circadian gene expression

Cited by 60 publications

References 50 publications

Circadian clock regulates the host response to Salmonella

Circadian clock regulates the host response to Salmonella

Immunometabolism: Is it under the eye of the clock?

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

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