The regulation effect of AMPK in immune related diseases

Wang, Jing; Li, Zhenyu; Gao, Li; Qi, Yanshuang; Zhu, Haibo; Qin, Xuemei

doi:10.1007/s11427-017-9169-6

Cited by 24 publications

(19 citation statements)

References 107 publications

(136 reference statements)

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“…In addition to its main anti-hyperglycemia effect, metformin has a protective effect against oxidative stress and inflammation [ 32 – 34 ]. Several studies have revealed that metformin is a potent activator of the AMPK signaling pathway, which mediates the reduction in the inflammatory response [ 35 – 37 ]. As reported in a recent study, metformin can prevent the development of antibiotic resistance and seems to be promising in terms of its application along with antibiotics during bacterial infections [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin activated AMPK signaling contributes to the alleviation of LPS-induced inflammatory responses in bovine mammary epithelial cells

et al. 2021

BMC Vet Res

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Background Lipopolysaccharides (LPS) derived from gram-negative bacterial are often regarded as primary inducer of bovine mammary inflammation. This study evaluated the biological response of metformin activated AMPK signaling on LPS-induced inflammatory responses and metabolic changes in primary bovine mammary epithelial cells (pbMEC). The pbMEC were exposed to either 3 mmol/L Metf. for 12 h as Metf. group (Metf.) or 2 μg/mL LPS for 6 h as LPS group (LPS). Cells pretreated with 3 mmol/L metformin for 12 h followed by washing and 2 μg/mL LPS exposure for 6 h were served as ML group (ML). PBS was added to cells as the control group (Con.). Results Pre-incubation with Metf. inhibited LPS-induced expression of pro-inflammatory genes (TNF, IL1B, IL6, CXCL8, MYD88 and TLR4) and proteins (IL-1β, TNF-α, NLRP3, Caspase1, ASC) and was accompanied by increased activation of AMPK signaling. Compared with the LPS group, phosphorylation of p65 and IκBα in the ML group were decreased and accumulation of NF-κB in the nucleus was significantly reduced by pretreatment with metformin. Metformin protects the cells from the increase of LPS-induced binding activity of NF-κB on both TNFA and IL1B promoters. Compared with the LPS group, genes (G6PC, PCK2) and proteins (SREBP1, SCD1) related to lipogenesis and carbohydrate metabolism were downregulated while catabolic ones (PPARA, ACSL1, Glut1, HK1) were upregulated in the ML group. Furthermore, increased acetylation of H3K14 by LPS challenge was reversed by pretreatment with metformin. Conclusion Altogether, our results indicated that pretreatment with metformin dampens LPS-induced inflammatory responses mediated in part by AMPK/NF-κB/NLRP3 signaling and modification of histone H3K14 deacetylation and metabolic changes.

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Section: Discussionmentioning

confidence: 99%

Metformin activated AMPK signaling contributes to the alleviation of LPS-induced inflammatory responses in bovine mammary epithelial cells

et al. 2021

BMC Vet Res

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“…These include NF-κβ and JAK/STAT, crucial drivers of maintaining energy balance, cytokine signaling, cell growth, and apoptosis (187). Interestingly, in the HLA-B27/hβ2 transgenic rat model where in vivo, prophylactic treatment of rats with rapamycin (m-TOR inhibitor) significantly inhibited the development and severity of inflammation in peripheral joints and spine (arthritis and spondylitis), with histological evidence of reduced bone erosions and new bone formation, all hallmarks of SpA (188). This is relevant in view of the fact that mTOR pathway has been indeed activated in SpA synovitis, and because mTOR blockade by rapamycin or metformin in mouse model stops osteoclastogenesis.…”

Section: Putting It All Togethermentioning

confidence: 99%

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

Harjaček

2021

Front. Med.

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Juvenile spondyloarthritis (jSpA) is a an umbrella term for heterogeneous group of related seronegative inflammatory disorders sharing common symptoms. Although it mainly affects children and adolescents, it often remains active during adulthood. Genetic and environmental factors are involved in its occurrence, although the exact underlying immunopathophysiology remains incompletely elucidated. Accumulated evidence suggests that, in affected patients, subclinical gut inflammation caused by intestinal dysbiosis, is pivotal to the future development of synovial–entheseal complex inflammation. While the predominant role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including jSpA, is firmly established, the role of the cytokine macrophage migration inhibitory factor (MIF) is generally overlooked. The purpose of this review is to discuss and emphasize the role of epigenetics, neuroendocrine pathways and the hypothalamic-pituitary (HPA) axis, and to propose a novel hypothesis of the role of decreased NLRP3 gene expression and possibly MIF in the early phases of jSpA development. The decreased NLRP3 gene expression in the latter, due to hypomethylation of promotor site, is (one of) the cause for inflammasome malfunction leading to gut dysbiosis observed in patients with early jSpA. In addition, we highlight the role of MIF in the complex innate, adaptive cellular and main effector cytokine network, Finally, since treatment of advanced bone pathology in SpA remains an unmet clinical need, I suggest possible new drug targets with the aim to ultimately improve treatment efficacy and long-term outcome of jSpA patients.

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“…As mentioned earlier, AMPK mediates autophagy and inflammation in osteoclasts, dendritic cells (DCs), macrophages and lymphocytes, while also Review participating in the regulation of immune-related diseases, such as rheumatoid arthritis, cancer, atherosclerosis and other inflammatory diseases (Wang et al, 2018). Metformin is a widely antidiabetic drug that depend on the activation of AMPK to inhibit the mitochondrial respiratory chain leading to an imbalance in energy regulation (Rena et al, 2013).…”

Section: The Use Of Agents and Clinical Drugs To Regulate Ampk-mediatmentioning

confidence: 99%

AMP‐activated protein kinase (AMPK) regulates autophagy, inflammation and immunity and contributes to osteoclast differentiation and functionabs

Tong

Ganta

Liu

2020

Biology of the Cell

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Osteoclasts are multinucleated giant cells, responsible for bone resorption. Osteoclast differentiation and function requires a series of cytokines to remove the old bone, which coordinates with the induction of bone remodelling by osteoblast‐mediated bone formation. Studies have demonstrated that AMP‐activated protein kinase (AMPK) play a negative regulatory role in osteoclast differentiation and function. Research involving AMPK, a nutrient and energy sensor, has primarily focused on osteoclast differentiation and function; thus, its role in autophagy, inflammation and immunity remains poorly understood. Autophagy is a conservative homoeostatic mechanism of eukaryotic cells, and response to osteoclast differentiation and function; however, how it interacts with inflammation remains unclear. Additionally, based on the regulatory function of different AMPK subunits for osteoclast differentiation and function, its activation is regulated by upstream factors to perform bone metabolism. This review summarises the critical role of AMPK‐mediated autophagy, inflammation and immunity by upstream and downstream signalling during receptor activator of nuclear factor kappa‐B ligand‐induced osteoclast differentiation and function. This pathway may provide therapeutic targets for bone‐related diseases, as well as function as a biomarker for bone homoeostasis.

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The regulation effect of AMPK in immune related diseases

Cited by 24 publications

References 107 publications

Metformin activated AMPK signaling contributes to the alleviation of LPS-induced inflammatory responses in bovine mammary epithelial cells

Metformin activated AMPK signaling contributes to the alleviation of LPS-induced inflammatory responses in bovine mammary epithelial cells

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

AMP‐activated protein kinase (AMPK) regulates autophagy, inflammation and immunity and contributes to osteoclast differentiation and functionabs

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