Nuclear factor-κB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep

Kubota, Takeshi; Kushikata, Tetsuya; Fang, Jidong; Krueger, James M.

doi:10.1152/ajpregu.2000.279.2.r404

Cited by 73 publications

(60 citation statements)

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“…Further, the Drosophila homologue of NF-κB, relish, is implicated in sleep regulation in that species (Williams et al 2007). Inhibition of NF-κ inhibits spontaneous NREMS and IL1β-induced sleep in rats (Kubota et al, 2000). However, loss of the p50 subunit of NF-κB in mice increases slow wave sleep and increases the homeostatic response to sleep loss (Jhaveri et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

Taishi

Churchill

et al. 2008

Brain Research

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Hypothalamic and cortical mRNA levels for cytokines such as interleukin-1α (IL1α), tumor necrosis factor alpha (TNFα), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are impacted by systemic treatments of IL1β and TNFα To investigate the time course of the effects of IL1β and TNFα on hypothalamic and cortical cytokine gene expression, we measured mRNA levels for IL1β, TNFα, interleukin-6 (IL-6), interleukin-10 (IL-10), IL1 receptor 1, BDNF, NGF, and glutamate decarboxylase-67 in vitro using hypothalamic and cortical primary cultures. IL1β and TNFα mRNA levels increased significantly in a dose-dependent fashion after exposure to either IL1β or TNFα. IL1β increased IL1β mRNA in both the hypothalamic and cortical cultures after 2-6 h while TNFα mRNA increased significantly within 30 min and continued to rise up to 2-6 h. Most of the other mRNAs showed significant changes independent of dose in vitro. In vivo, intracerebroventricular (icv) injection of IL1β or TNFα also significantly increased IL1β, TNFα and IL6 mRNA levels in the hypothalamus and cortex. IL1β icv, but not TNFα increased NGF mRNA levels in both these areas. Results support the hypothesis that centrally active doses of IL1β and TNFα enhance their own mRNA levels as well as affect mRNA levels for other neuronal growth factors.

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Section: Discussionmentioning

confidence: 99%

Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

Taishi

Churchill

et al. 2008

Brain Research

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“…ECoG electrodes were placed over the frontal and parietal cortices as previously described (30). The leads from the ECoG electrodes were routed to a Teflon pedestal, which was attached to the skull with dental cement.…”

Section: Methodsmentioning

confidence: 99%

Circadian desynchronization of core body temperature and sleep stages in the rat

Cambras

Weller

Anglès-Pujoràs

et al. 2007

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

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Proper functioning of the human circadian timing system is crucial to physical and mental health. Much of what we know about this system is based on experimental protocols that induce the desynchronization of behavioral and physiological rhythms within individual subjects, but the neural (or extraneural) substrates for such desynchronization are unknown. We have developed an animal model of human internal desynchrony in which rats are exposed to artificially short (22-h) light-dark cycles. Under these conditions, locomotor activity, sleep-wake, and slow-wave sleep (SWS) exhibit two rhythms within individual animals, one entrained to the 22-h light-dark cycle and the other free-running with a period >24 h ( >24 h). Whereas core body temperature showed two rhythms as well, further analysis indicates this variable oscillates more according to the >24 h rhythm than to the 22-h rhythm, and that this oscillation is due to an activity-independent circadian regulation. Paradoxical sleep (PS), on the other hand, shows only one freerunning rhythm. Our results show that, similarly to humans, (i) circadian rhythms can be internally dissociated in a controlled and predictable manner in the rat and (ii) the circadian rhythms of sleep-wake and SWS can be desynchronized from the rhythms of PS and core body temperature within individual animals. This model now allows for a deeper understanding of the human timekeeping mechanism, for testing potential therapies for circadian dysrhythmias, and for studying the biology of PS and SWS states in a neurologically intact model.

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“…L-PGDS gene is involved in the regulation of NREM sleep (9), and IL-1␤ is one of the somnogenic substances and is involved in NREM sleep induction through the activation of NF-B (27)(28)(29). Furthermore, IL-1␤ receptor was detected in high concentration in the leptomeninges (63,64).…”

Section: Fig 7 Binding Of Nuclear Factors To the Two Nf-b Elementsmentioning

confidence: 99%

“…On the other hand, the L-PGDS level in the rat CSF was increased by the administration of a proinflammatory cytokine, interleukin (IL)-1␤ (26). IL-1␤ and tumor necrosis factor-␣ activate the NF-B system (27) to elicit somnogenic activities (28,29). The sleep-inducing effects of IL-1␤ and tumor necrosis factor-␣ were proposed to be mediated by L-PGDS, because these effects were inhibited by administration of inhibitors of PG synthesis to animals (29).…”

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confidence: 99%

Regulation of Lipocalin-type Prostaglandin D Synthase Gene Expression by Hes-1 through E-box and Interleukin-1β via Two NF-κB Elements in Rat Leptomeningeal Cells

Fujimori¹,

Fujitani²,

Kadoyama³

et al. 2003

Journal of Biological Chemistry

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The promoter function of the rat lipocalin-type prostaglandin D synthase (L-PGDS) gene was characterized in primary cultures of leptomeningeal cells prepared from the neonatal rat brain. Luciferase reporter assays with deletion and site-directed mutation of the promoter region (؊1250 to ؉77) showed that an AP-2 element at ؊109 was required for activation and an E-box at ؉57, for repression. Binding of nuclear factors to each of these cis-elements was demonstrated by an electrophoretic mobility shift assay. Several components of the Notch-Hes signaling pathway, Jagged, Notch1, Notch3, and Hes-1, were expressed in the leptomeningeal cells. Human Hes-1 co-expressed in the leptomeningeal cells bound to the E-box of the rat L-PGDS gene, and repressed the promoter activity of the rat L-PGDS gene in a dose-dependent manner. The L-PGDS gene expression was up-regulated slowly by interleukin-1␤ to the maximum level at 24 h. The reporter assay with deletion and mutation revealed that two NF-B elements at ؊1106 and ؊291 were essential for this up-regulation. Binding of two NF-B subunits, p65 and c-Rel, to these two NF-B elements occurred after the interleukin-1␤ treatment. Therefore, the L-PGDS gene is the first gene identified as the target for the Notch-Hes signal through the E-box among a variety of genes involved in the prostanoid biosynthesis, classified to the lipocalin family, and expressed in the leptomeninges. Moreover, the L-PGDS gene is a unique gene that is activated slowly by the NF-B system. Lipocalin-type prostaglandin (PG)1 D synthase (L-PGDS) was first identified in the rat brain as an enzyme that catalyzes the conversion to PGD 2 from PGH 2 , the latter being a common precursor of all prostanoids (1). Later, L-PGDS was found to be identical to ␤-trace (2, 3), which had been identified earlier (4) as the major protein in human cerebrospinal fluid (CSF). PGD 2 is a major prostanoid in the brain, known as the most potent endogenous somnogenic substance thus far identified (5), and is involved in various physiological events such as regulation of sleep and pain responses (5-8). Because human L-PGDS-overexpressing transgenic mice (9) and L-PGDS-gene knock-out mice (10, 11) showed abnormality in the regulation of non-rapid eye movement (NREM) sleep and pain responses, PGD 2 produced by L-PGDS is thought to play important roles in the regulation of NREM sleep and pain sensation in the central nervous system. Alternatively L-PGDS binds small lipophilic molecules such as retinal and retinoic acid (K d ϭ 70 -80 nM) (12) and biliverdin and bilirubin (K d ϭ 33-37 nM) (13) with affinities higher than those of other members of the lipocalin family. Therefore, L-PGDS is a unique bifunctional protein acting as a PGD 2 -producing enzyme and as a lipophilic molecule-binding protein (6 -8).L-PGDS is expressed abundantly in the human heart (14), the male genital organs (15-17), and the central nervous system (18 -20) of various mammals. In the brain, this enzyme is expressed dominantly in the leptomeninges, chroid plexus, and...

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Nuclear factor-κB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep

Cited by 73 publications

References 50 publications

Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

Circadian desynchronization of core body temperature and sleep stages in the rat

Regulation of Lipocalin-type Prostaglandin D Synthase Gene Expression by Hes-1 through E-box and Interleukin-1β via Two NF-κB Elements in Rat Leptomeningeal Cells

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