NF-κB signaling as a driver of ageing

Osorio, Fernando G.; Soria‐Valles, Clara; Santiago‐Fernández, Olaya; Freije, José M.P.

doi:10.1016/bs.ircmb.2016.04.003

Cited by 57 publications

(44 citation statements)

References 204 publications

(229 reference statements)

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“…Cathepsin L was shown to have a dual role in NF‐κB regulation, being involved in the activation as well as the suppression of NF‐κB activity . Current evidence supports the idea that increased activation of NF‐κB, as a key transcriptional regulator of genes involved in processes such as inflammation and apoptosis, is a driving force behind the ageing process . It is also known that AGE exposure leads to NF‐κB activation .…”

Section: Discussionmentioning

confidence: 74%

Advanced glycation end products‐related modulation of cathepsin L and NF‐κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα

Sharif

Mahmud

Kay

et al. 2018

J Cellular Molecular Medi

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The retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age‐related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)—known to accumulate on the ageing RPE's underlying Bruch's membrane in situ—on both key lysosomal cathepsins and NF‐κB signalling in RPE. Cathepsin L activity and NF‐κB effector levels decreased significantly following 2‐week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE‐related change of NF‐κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE‐exposed cells had significantly higher ratio of phospho‐p65(Ser536)/total p65 compared to non‐AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE‐related activation of NF‐κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF‐κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para‐inflammatory) mechanism but renders them more responsive to pro‐inflammatory stimuli.

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Section: Discussionmentioning

confidence: 74%

Advanced glycation end products‐related modulation of cathepsin L and NF‐κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα

Sharif

Mahmud

Kay

et al. 2018

J Cellular Molecular Medi

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“…Reciprocally, such alterations of circadian rhythms were also observed during chronic inflammation (Guo et al 2015). More broadly, other conditions that alter circadian rhythms, such as aging or sleep deprivation, are also associated with activation of the NF-κB pathway (Osorio et al 2016), suggesting a general link between inflammation and disruption of circadian timekeeping.…”

mentioning

confidence: 91%

Cross-regulatory circuits linking inflammation, high-fat diet, and the circadian clock

2018

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Mammalian physiology resonates with the daily changes in the external environment, allowing processes such as rest–activity cycles, metabolism, and body temperature to synchronize with daily changes in the surroundings. Studies have identified the molecular underpinnings of robust oscillations in gene expression occurring over the 24-h day, but how acute or chronic perturbations modulate gene expression rhythms, physiology, and behavior is still relatively unknown. In this issue of Genes & Development, Hong and colleagues (pp. 1367–1379) studied how acute and chronic inflammation interacts with the circadian clock. They found that NF-κB signaling can modify chromatin states and modulate expression of genes in the core clock network as well as circadian locomotor behavior. Interestingly, a high-fat diet (HFD) fed to mice also triggers this inflammation pathway, suggesting that cross-regulatory circuits link inflammation, HFD, and the circadian clock.

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“…Considering the underlying molecular mechanisms involved in these processes, we focused our attention on the well-established fact that activated nuclear factor-κB (NF-κB) is a major factor in the pathogenesis of aging-induced, low-grade chronic inflammation [13–20]. At the same time, NF-κB is a key component of the body responses to acute inflammation via its main regulatory role in the production of numerous cytokines [21–26].…”

Section: Introductionmentioning

confidence: 99%

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation

Nizamutdinova

Dusio

Gasheva

et al. 2016

Aging

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This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics.

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NF-κB signaling as a driver of ageing

Cited by 57 publications

References 204 publications

Advanced glycation end products‐related modulation of cathepsin L and NF‐κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα

Advanced glycation end products‐related modulation of cathepsin L and NF‐κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα

Cross-regulatory circuits linking inflammation, high-fat diet, and the circadian clock

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation

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