NF‐κB signalling is involved in immune‐modulation, but not basal functioning, of the mouse suprachiasmatic circadian clock

Abstract

Circadian rhythms are recurring near-24 hour patterns driven by an endogenous circadian timekeeping system. The master pacemaker in this system is the hypothalamic suprachiasmatic nucleus (SCN). Recently interest has been drawn to how the SCN clock responds to immune system stimulation. A major signalling component in the immune system is nuclear factor (NF)-κB. In the present study we examined the role of NF-κB in SCN function. Whilst serum shocked fibroblasts showed rhythmic nuclear localisation of p65 and p65-dependent transcription, there were no circadian changes in the SCN in expression of the NF-κB components p65, c-Rel, p-IκB or p-IKK. Chronic treatment with the NF-κB inhibitor PDTC did not impact on circadian or diurnal rhythms. Phase-shifting light pulses did not impact on SCN expression of p65, and PDTC treatment did not attenuate the behavioural or molecular response to light pulses. Peripheral treatment with lipopolysaccharide resulted in increased NF-κB component expression in the SCN. In vitro experiments with SCN slice cultures showed that treatment with NF-κB inhibitors did not markedly alter rhythmic changes in PER2::LUC expression. Further, SCN slices from nf-κb::luc mice did not show any evidence for circadian rhythms in NF-κB-mediated transcription. Experiments utilising older mice (~16 months old) showed that SCN treatment in vitro with PDTC resulted in increased amplitude of rhythmic PER2::LUC expression, and LPS treatment resulted in altered PER2::LUC rhythm acrophase. Overall, we interpret our results as providing evidence for the involvement of NF-κB in the suprachiasmatic circadian clock following immune stimulation, but not under basal conditions.

Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: A therapeutic target to reduce intestinal inflammation

“…Moreover, the NF‐κB component also regulates neuroimmune responses. NF‐κB signaling is vital in circadian timing of peripheral cells, which indicates that NF‐κB plays a role in regulating clock processes of CNS and participates in the communication of the brain‐gut axis . This reaction of microbial rhythms stimulates the immune system provides high evidence to support the view that the interaction between melatonin and microbial signaling acts as a prominent role in maintaining the stability of GI function by regulating the circadian system of the host …”

“…Changes in antioxidative capacity may be another means by which melatonin affects B cells. In the immune system, nitric oxide (NO) is an important inhibitory factor for human lymphocyte proliferation . Melatonin inhibits inducible nitric oxide synthase (iNOS) activity and LPS‐induced NO production in wild‐type mice .…”

“…Melatonin via NF‐κB signaling is synergistically involved in immune modulation . It also influences the circadian clock of microbial metabolism . The circadian rhythm exerts critical effects in keeping the homeostasis and health.…”

Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms

“…To obtain circadian parameters including phase, period length, rhythm amplitude, and damping rate, the LumiCycle Analysis program (Actimetrics) and Actogram J software was used. Luminometry data was detrended and smoothed with a rolling 3 h average as previously described [29,30]. Circadian parameters were derived from cosinor analysis and period was determined from Lomb-Scargle periodograms analysis.…”

Circadian rhythm and atherosclerosis (Review)

“…An increasing number of studies have indicated that the molecular clock has an important role in almost all metabolic processes in organisms. Furthermore, disruptions to the circadian rhythm may lead to cardiovascular diseases ( 13 ), type 2 diabetes ( 14 ) and immune system diseases ( 15 ).…”