Black raspberry anthocyanins protect BV2 microglia from LPS-induced inflammation through down-regulating NOX2/TXNIP/NLRP3 signaling

2021 ◽  
pp. 1-15
Author(s):  
Teng Mu ◽  
Yang Guan ◽  
Tianqiao Chen ◽  
Shuning Wang ◽  
Mei Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Receptor Protein ◽  
Black Raspberry ◽  
Interleukin 18 ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Immunological Mechanisms ◽  
Signaling Axis ◽  
Bv2 Microglia ◽  
Excessive Activation

BACKGROUND: Increasing evidence has established neuroinflammation as the hallmark of neurodegenerative disorders such as Alzheimer’s disease (AD). However, despite the underlying immunological mechanisms are far from being understood, the involvement of excessive activation of microglia is attracting more and more attention. OBJECTIVE: In the present study, we investigated the protective effect of black raspberry (BRB) anthocyanins on LPS-induced neuroinflammation in BV2 microglia. METHODS: LPS-induced mouse BV2 microglia were treated with black raspberry anthocyanins and the levels of NO, ROS, IL-1β and IL-18 produced by the cells were measured to determine the extent of oxidative stress and inflammatory response. RESULTS: The results showed that BRB anthocyanins reduced the production of ROS in LPS-induced BV2 microglia by down-regulating the level of NOX2 and its downstream factors, including thioredoxin-interacting protein (TXNIP) and NOD-like receptor protein 3 (NLRP3) inflammasome. Furthermore, BRB anthocyanins inhibited the secretion of Interleukin-18 (IL-18) and Interleukin-1β (IL-1β), eventually attenuating the LPS-induced inflammatory response of BV2 microglia. CONCLUSIONS: BRB anthocyanins might play an important neuroprotective role in inflammation-related neurodegenerative disease, potentially, by down-regulating the NOX2 /TXNIP/ NLRP3 signaling axis in brain microglia.

scholarly journals NLRC4 Mutation in flagellin-derived peptide CBLB502 ligand-binding domain reduces the inflammatory response but not radioprotective activity

2019 ◽  
Vol 60 (6) ◽  
pp. 780-785
Author(s):  
Lili Lai ◽  
Ganggang Yang ◽  
Xuelian Yao ◽  
Lei Wang ◽  
Yiqun Zhan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Nuclear Factor Kappa B ◽  
Binding Domain ◽  
Receptor Protein ◽  
Toll Like Receptor ◽  
Interleukin 18 ◽  
Radioprotective Activity ◽  
Binding Domains ◽  
Molecular Pattern ◽  
Toll Like Receptor 5

ABSTRACT Bacterial flagellin is a pathogen-associated molecular pattern recognized by surface-localized Toll-like receptor 5 (TLR5) and cytosolic NOD-like receptor protein 4 (NLRC4). CBLB502, derived from Salmonella flagellin, exhibits high radioprotective efficacy in mice and primates by regulating TLR5 and the nuclear factor kappa B (NF-κB) signaling pathway. In this study, we examined the effects of CBLB502 and mutations in its NLRC4- and TLR5-binding domains on radioprotective efficacy and the immune inflammatory response. The results showed that CBLB502 mutation with I213A in the TLR5-binding domain significantly reduced NF-κB activity and radioprotective activity, whereas CBLB502 mutation with L292A in NLRC4-binding domain did not. Additionally, CBLB502 with both mutations greatly reduced NF-κB activity and eliminated radioprotection in mice. In contrast, NLRC4-binding domain mutation reduced the secretion of inflammatory interleukin-1β and interleukin-18. CBLB502 exerts its radioprotective effects through both the TLR5 and NLRC4 pathways. Additionally, deletion in the NLRC4-binding domain did not reduce radioprotective activity but reduced the inflammatory response.

scholarly journals Targeting NLRP3 Inflammasome in Translational Treatment of Nervous System Diseases: An Update

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingying Yu ◽  
Tingting Zhao ◽  
Molin Liu ◽  
Duo Cao ◽  
Jiaxin Li ◽  
...  
Keyword(s):  
Nervous System ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Neurological Diseases ◽  
Interleukin 1Β ◽  
Receptor Protein ◽  
Inflammatory Factors ◽  
Interleukin 18 ◽  
Neuroinflammatory Response ◽  
Molecular Patterns

Neuroinflammatory response is the immune response mechanism of the innate immune system of the central nervous system. Both primary and secondary injury can activate neuroinflammatory response. Among them, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a key role in the inflammatory response of the central system. Inflammasome is a type of pattern recognition receptor, a cytoplasmic polyprotein complex composed of members of the Nod-like receptor (NLR) family and members of the pyrin and HIN domain (PYHIN) family, which can be affected by a variety of pathogen-related molecular patterns or damage-related molecular patterns are activated. As one of the research hotspots in the field of medical research in recent years, there are increasing researches on immune function abnormalities in the onset of neurological diseases such as depression, AD, ischemic brain injury and cerebral infarction, the NLRP3 inflammasome causes the activated caspase-1 to cleave pre-interleukin-1β and pre-interleukin-18 into mature interleukin-1β and interleukin-18, in turn, a large number of inflammatory factors are produced, which participate in the occurrence and development of the above-mentioned diseases. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response, promote the survival of nerve cells, and achieve neuroprotective effects. This article reviews NLRP3 inflammasome’s role in neurological diseases and related regulatory mechanisms, which providing references for future research in this field.

scholarly journals Hydrogen sulfide mitigates myocardial inflammation by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome activation in diabetic rats

2020 ◽  
Vol 245 (3) ◽  
pp. 221-230 ◽  
Author(s):  
Qiang Jia ◽  
Shomaila Mehmood ◽  
Xiaofen Liu ◽  
Shanfeng Ma ◽  
Rui Yang
Keyword(s):  
Hydrogen Sulfide ◽  
Nlrp3 Inflammasome ◽  
Fasting Blood Glucose ◽  
Nucleotide Binding ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Interacting Protein ◽  
Sodium Hydrosulfide ◽  
Thioredoxin Interacting Protein ◽  
Oligomerization Domain

Inflammation plays a crucial part in hyperglycemia-induced myocardial damage. Hydrogen sulfide has been found to possess multiple biological activities in previous studies. This study investigated whether hydrogen sulfide conferred cardiac protection against damage in a diabetic rat model by inhibiting nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome activation. Male animals were assigned to control, streptozotocin, streptozotocin + sodium hydrosulfide, and streptozotocin + DL-propargylglycine groups. Animals in the three streptozotocin groups were administrated 55 mg/kg streptozotocin by intraperitoneal injection. Streptozotocin + sodium hydrosulfide and streptozotocin + propargylglycine groups were treated with sodium hydrosulfide (56 μmol/kg) and propargylglycine (40 mg/kg), respectively, for four weeks. Estimation of fasting blood glucose, heart-weight/body-weight, cardiac function, and histopathological analysis, and measurement of myocardial enzymes were done to evaluate the degree of cardiac injury. In order to investigate the redox changes, the levels of total antioxidant capacity, malondialdehyde and lipid peroxidation, and the activities of superoxide dismutase, catalase, and glutathione peroxidase were assessed; the protein expression levels of Thioredoxin and Thioredoxin-interacting protein were measured in myocardial tissue. In addition, inflammatory reactions were assessed by measuring the concentration levels of interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-18 in serum and the expression levels of NLRP3 inflammasome complex-associated proteins in cardiac tissue. In the heart, hyperglycemia significantly induced cardiac dysfunction and injury, redox perturbation, and aggravation of inflammatory reactions. However, except for fasting blood glucose, treatment with sodium hydrosulfide significantly ameliorated these alterations, whereas treatment with propargylglycine further aggravated these alterations. This study highlights the protective properties of hydrogen sulfide against hyperglycemia-induced cardiac injury, and its possible mechanism was shown to involve negative regulation of Thioredoxin-interacting protein-mediated NLRP3 inflammasome activation. Impact statement Diabetic cardiomyopathy is a serious complication of diabetic patients, accompanied by chronic inflammation. The nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome complex is involved in the progression of the inflammatory response of diabetes, including diabetic cardiomyopathy. Hydrogen sulfide (H2S) is a novel endogenous gas messenger. Several pieces of evidence have exhibited that H2S exerts anti-oxidant and anti-inflammatory activities against hyperglycemia-induced myocardial injury, but the mechanism remains unclear. The current study indicated that H2S protected the myocardium against hyperglycemia-induced injury by preventing Thioredoxin-interacting protein (TXNIP)-mediated NLRP3 inflammasome complex activation. The inhibition of TXNIP-mediated NLRP3 inflammasome complex would be an efficient therapy for H2S treatment in diabetic cardiomyocytes.

scholarly journals Deletion of Thioredoxin-Interacting Protein (TXNIP) Abrogates High Fat Diet-Induced Retinal Leukostasis, Barrier Dysfunction and Microvascular Degeneration in a Mouse Obesity Model

2020 ◽  
Vol 21 (11) ◽  
pp. 3983 ◽  
Author(s):  
Islam N. Mohamed ◽  
Nader Sheibani ◽  
Azza B. El-Remessy
Keyword(s):  
Adhesion Molecules ◽  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
The Impact

We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and interaction with thioredoxin-interacting protein (TXNIP). Here, the specific contribution of TXNIP and the impact of HFD on retinal leukostasis, barrier dysfunction and microvascular degeneration were investigated. Wild-type (WT) and TXNIP knockout (TKO) mice were fed with normal diet or 60% HFD for 8–18 weeks. TXNIP was overexpressed or silenced in human retinal endothelial cells (REC). At 8 weeks, HFD significantly induced retinal leukostasis and breakdown of the blood–retina barrier in WT mice, but not in TKO mice. In parallel, HFD also induced retinal expression of adhesion molecules and cleaved IL-1β in WT mice, which were also abrogated in TKO mice. In culture, TXNIP overexpression induced NLRP3, IL-1β, and adhesion molecules expression, while TXNIP silencing inhibited them. Blocking the IL-1β receptor significantly suppressed TXNIP-induced expression of NLRP3-inflammasome and adhesion molecules in HREC. Ex-vivo assay showed that leukocytes isolated from WT-HFD, but not from TKO-HFD, induced leukostasis and cell death. At 18 weeks, HFD triggered development of degenerated (acellular) capillaries and decreased branching density in WT but not in TKO mice. Together, HFD-induced obesity triggered early retinal leukostasis and microvascular dysfunction at least in part via TXNIP-NLRP3-inflammasome activation.

scholarly journals The Critical Role of Thioredoxin-Interacting Protein in Shear-Related Inflammatory Response in Diabetes

2016 ◽  
Vol 25 ◽  
pp. S91
Author(s):  
J. Ciofani ◽  
J. Yuan ◽  
P. Simpson ◽  
E. King ◽  
L. Khoo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

miR-125b enhances metastasis and progression of cancer via the TXNIP and HIF1α pathway in pancreatic cancer

2021 ◽  
pp. 1-12
Author(s):  
Pengli Wang ◽  
Dan Zheng ◽  
Hongyang Qi ◽  
Qi Gao
Keyword(s):  
Pancreatic Cancer ◽  
Hypoxia Inducible Factor ◽  
Immunofluorescence Assay ◽  
Luciferase Assay ◽  
Interacting Protein ◽  
Over Expression ◽  
Thioredoxin Interacting Protein ◽  
Cellular Processes ◽  
And Migration

BACKGROUND: MicroRNAs (miRNAs) play potential role in the development of various types of cancer conditions including pancreatic cancer (PC) targeting several cellular processes. Present study was aimed to evaluate function of miR-125b and the mechanism involved in PC. METHODS: Cell migration, MTT and BrdU study was done to establish the migration capability, cell viability and cell proliferation respectively. Binding sites for miR-125b were recognized by luciferase assay, expression of protein by western blot and immunofluorescence assay. In vivo study was done by BALB/c nude xenograft mice for evaluating the function of miR-125b. RESULTS: The study showed that expression of miR-125b was elevated in PC cells and tissues, and was correlated to proliferation and migration of cells. Also, over-expression of miR-125b encouraged migration, metastasis and proliferation of BxPC-3 cells, the suppression reversed it. We also noticed that thioredoxin-interacting protein (TXNIP) was the potential target of miR-125b. The outcomes also suggested that miR-125b governed the expression of TXNIP inversely via directly attaching to the 3′-UTR activating hypoxia-inducible factor 1α (HIF1α). Looking into the relation between HIF1α and TXNIP, we discovered that TXNIP caused the degradation and export of HIF1α by making a complex with it. CONCLUSION: The miR-125b-TXNIP-HIF1α pathway may serve useful strategy for diagnosing and treating PC.

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