AMPK is essential for IL-10 expression and for maintaining balance between inflammatory and cytoprotective signaling

Guragain, Diwakar; Gurung, Pallavi; Chang, Jae‐Hoon; Katila, Nikita; Chang, Hyeun Wook; Jeong, Byeong‐Seon; Choi, Dong‐Young; Kim, Jung-Ae

doi:10.1016/j.bbagen.2020.129631

Cited by 14 publications

(13 citation statements)

References 57 publications

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“…In addition, we observed that increased 5-HT in the colon reduced the expression of p-AMPKα, a known upstream regulator of mTOR ( 44 ). Similar to our findings, Guragain et al ( 45 ) reported that 5-HT treatment of colon epithelial cells induced dephosphorylation of AMPKα in a dose-dependent manner. This suggests that increased 5-HT inhibits phosphorylation of AMPKα, leading to activation of mTOR, since it is known that AMPK regulates mTORC1 signaling ( 6 , 44 ).…”

Section: Discussionsupporting

confidence: 93%

Disruption of autophagy by increased 5-HT alters gut microbiota and enhances susceptibility to experimental colitis and Crohn’s disease

et al. 2021

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Section: Discussionsupporting

confidence: 93%

Disruption of autophagy by increased 5-HT alters gut microbiota and enhances susceptibility to experimental colitis and Crohn’s disease

et al. 2021

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“…Hyperactivation of the inflammatory response is associated with DSS-induced colitis. AMPK is known for its anti-inflammatory effects [ 35 ]. GRP supplementation elevated AMPK activity as shown by increased AMPK phosphorylation ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice

Tian

Sun

et al. 2022

Antioxidants

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As the prevalence of inflammatory bowel diseases (IBD) rises, the etiology of IBD draws increasing attention. Glucoraphanin (GRP), enriched in cruciferous vegetables, is a precursor of sulforaphane, known to have anti-inflammatory and antioxidative effects. We hypothesized that dietary GRP supplementation can prevent mitochondrial dysfunction and oxidative stress in an acute colitis mouse model induced by dextran sulfate sodium (DSS). Eight-week-old mice were fed a regular rodent diet either supplemented with or without GRP. After 4 weeks of dietary treatments, half of the mice within each dietary group were subjected to 2.5% DSS treatment to induce colitis. Dietary GRP decreased DSS-induced body weight loss, disease activity index, and colon shortening. Glucoraphanin supplementation protected the colonic histological structure, suppressed inflammatory cytokines, interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α), and reduced macrophage infiltration in colonic tissues. Consistently, dietary GRP activated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, and nuclear factor erythroid 2-related factor 2 (NRF2) pathways in the colonic tissues of DSS-treated mice, which was associated with increased mitochondrial DNA and decreased content of the oxidative product 8-hydroxydeoxyguanosine (8-OHDG), a nucleotide oxidative product of DNA. In conclusion, dietary GRP attenuated mitochondrial dysfunction, inflammatory response, and oxidative stress induced by DSS, suggesting that dietary GRP provides a dietary strategy to alleviate IBD symptoms.

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“…In line with our results, Bai et al showed that the pharmacological stimulation of AMPK with acadesine reduced NF-kB activation in colonic tissues, resulting in a marked decrease in proinflammatory cytokines (TNF, IL-17, IL-12, IL-23, IFN-γ) and a down-regulation of iNOS expression in intestinal macrophages [12]. Interestingly, a set of studies showed that the pharmacological stimulation of AMPK elicited the re-polarization of leukocyte phenotypes inducing programs of anti-inflammatory gene expression, including IL-10 [54,55].…”

Section: Discussionmentioning

confidence: 99%

Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation

Antonioli

Pellegrini

Fornai

et al. 2021

IJMS

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Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats. A set of experiments evaluated the ability of FA5 to activate AMPK and to compare the efficacy of FA5 with ACA in an experimental model of colitis. The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters. In in vitro experiments, FA5 induced phosphorylation, and thus the activation, of AMPK, contextually to the activation of SIRT-1. In vivo, FA5 counteracted the increase in spleen weight, improved the colon length, ameliorated macroscopic damage score, and reduced TNF and MDA tissue levels in DNBS-treated rats. Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation.

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AMPK is essential for IL-10 expression and for maintaining balance between inflammatory and cytoprotective signaling

Cited by 14 publications

References 57 publications

Disruption of autophagy by increased 5-HT alters gut microbiota and enhances susceptibility to experimental colitis and Crohn’s disease

Disruption of autophagy by increased 5-HT alters gut microbiota and enhances susceptibility to experimental colitis and Crohn’s disease

Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice

Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation

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