Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of SIGIRR to Inhibit NF-κB Signaling Pathway

Xu, Xiaomeng; Ning, Yuping; Wang, Wen‐Juan; Liu, Jieqiong; Bai, Xueyuan; Sun, Xuefeng; Cai, Guangyan; Chen, Xiangmei

doi:10.1159/000430248

Cited by 29 publications

(18 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, TLR4 and TLR9 were both downregulated as were numerous CCL chemokines in CTL CR mice, but only TLR9 and CCL1, 2, 20, and 22 met our cut-off parameters for statistical significance. These data support previous reports investigating the effects of long-term CR on NF-kB signaling (44) and inflammatory cytokines (45). The development of fibrosis and cirrhosis are established risk factors for the development of liver cancers including HCC (46).…”

Section: Discussionsupporting

confidence: 90%

Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice

Ploeger

Manivel

Boatner

et al. 2017

Cancer Prevention Research

View full text Add to dashboard Cite

Caloric restriction (CR) and endurance exercise elicit wide-ranging health benefits including reduced risk of select cancers. In addition, diet composition influences oncogenesis, although its interactions with exercise and CR are not well understood. Therefore, to investigate the potential interactions between diet and lifestyle interventions on liver tumorigenesis, the carcinogen diethylnitrosamine was administered to 72 male C57Bl/6 mice that were subsequently fed diets enriched with lard (CTL) or olive oil and were further stratified to voluntary wheel running (Ex) or 30% CR for 49 weeks. Although Ex and diet composition did not influence liver oncogenesis, CR prevented hepatic tumor formation. In addition, CR reduced steatosis, hepatocyte ballooning, inflammation, and immune cell infiltration, all of which are hallmarks in the progression of nonalcoholic fatty liver disease to liver tumorigenesis. RNA sequencing of nontransformed liver tissues from CR mice revealed changes in metabolic pathways and reduced inflammation, cytokine production, stellate cell activation and migration, and genes associated with liver injury and oncogenesis. These data demonstrate that CR protects against steatosis, liver inflammation, and liver injury and is a robust deterrent of carcinogen-induced hepatic oncogenesis..

show abstract

Section: Discussionsupporting

confidence: 90%

Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice

Ploeger

Manivel

Boatner

et al. 2017

Cancer Prevention Research

View full text Add to dashboard Cite

show abstract

“…Another study revealed that andrographolide could possess anti-cancer properties capable of modulating the TLR4/NF-κB signaling pathway in insulinoma [14]. The inflammatory response might be alleviated by single immunoglobulin IL-1-related receptor via blockade of the TLR4/NF-κB signaling pathway [15]. Despite the fact that the TLR4/NF-κB pathway has been extensively reviewed, studies investigating its potential effect on GERD, particularly on esophageal mucosal injury, are rare.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease

Yu¹,

Wang²,

Zhang³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Numerous studies have highlighted the activation of NF-κB in the esophageal mucosa during the early stages of gastroesophageal reflux disease (GERD). The present study aimed to investigate the role of the TLR4/NF-κB signaling pathway in GERD rat models. Methods: Wistar rats (n = 60) were recruited to establish a GERD animal model. Distal esophageal pH was assessed, followed by determination of the contents of thiobarbituric acid-reactive species (TBARS) and reactive oxygen species (ROS) in esophageal mucosa homogenate. ELISA was employed to detect the levels of inflammatory factors (IL-6, IL-8, IL-10 and TNF-α) in esophageal mucosa. The expression of MMP-3, MPP-9, Cldn1 and Cldn4 was determined by immunohistochemistry. RT-qPCR and western blot analysis were applied to evaluate the protein expressions in TLR4/NF-κB signaling pathway, while TUNEL staining was utilized to examine the apoptosis rate in the esophageal mucosal tissues. Results: Distal esophageal pH of the rats was higher in the GERD + PDTC group than in other groups. Levels of inflammatory factors in esophageal mucosal tissues were downregulated with the inhibition of NF-κB, which was determined to be associated with the decreased contents of TBARS and ROS. Moreover, decreased MMP-3 and MPP-9 in addition to elevated Cldn1 and Cldn4 were detected in the esophageal mucosa as a result of the inactivation of NF-κB. The TLR4/NF-κB signaling pathway-related proteins (TLR4, NF-κB and IκBα); the rate of apoptosis was demonstrated to be suppressed in the GERD + PDTC group, while inactivating NF-κB was found to alleviate the tissue damage observed in the esophageal mucosa. Conclusion: The key findings of the current study demonstrate that the inactivation of the TLR4/NF-κB signaling pathway alleviates oxidative stress injury and promotes the repair of esophageal mucosal injury among rats with GERD, highlighting a potential novel GERD mechanism.

show abstract

“…Regulation of IL‐1R8 is therefore relevant for the effects of IL‐37. Evidence reveals that expression of IL‐1R8 decreases with age in rats but that when rats were subjected to a calorie restricted diet, expression of IL‐1R8 increased . In that study, caloric restriction resulted in decreased NF‐κB expression.…”

Section: Mechanism Of Action: Il‐37 Receptorsmentioning

confidence: 75%

“…B). IL‐1R8 overexpression decreases the expression of MyD88, IL‐1 receptor‐associated kinase 4 (IRAK4), and tumor necrosis factor receptor‐associated factor 6 (TRAF6) . As shown in Figure B, IL‐1R8 functions as a sink for MyD88, depriving MyD88 from binding to the native TIR domain, resulting in a weak or no signal.…”

Section: Mechanism Of Action: Il‐37 Receptorsmentioning

confidence: 99%

Suppression of innate inflammation and immunity by interleukin‐37

et al. 2016

View full text Add to dashboard Cite

IL-37 is unique in the IL-1 family in that unlike other members of the family, IL-37 broadly suppresses innate immunity. IL-37 can be elevated in humans with inflammatory and autoimmune diseases where it likely functions to limit inflammation. Transgenic mice expressing human IL-37 (IL37-tg) exhibit less severe inflammation in models of endotoxin shock, colitis, myocardial infarction, lung and spinal cord injury. IL37-tg mice have reduced antigen-specific responses and dendritic cells (DCs) from these mice exhibit characteristics of tolerogenic DCs. Compared to aging wild-type (WT) mice, aging IL37-tg mice are protected against B-cell leukemogenesis and heart failure. Treatment of WT mice with recombinant human IL-37 has been shown to be protective in several models of inflammation and injury. IL-37 binds to the IL-18 receptor but then recruits the orphan IL-1R8 (formerly TIR8 or Sin order function as an inhibitor. Here we review the discovery of IL-37, its production, release and mechanisms by which IL-37 reduces inflammation and suppresses immune responses. The data reviewed here suggest a therapeutic potential for IL-37.

show abstract

Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of SIGIRR to Inhibit NF-κB Signaling Pathway

Cited by 29 publications

References 35 publications

Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice

Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice

Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease

Suppression of innate inflammation and immunity by interleukin‐37

Contact Info

Product

Resources

About