scholarly journals HMGB1-induced NLRP3 Inflammasome Participating in Platelet Activation and Thrombocytopenia in Heatstroke

2021 ◽  
Author(s):  
Huimei Yin ◽  
Ming Wu ◽  
Yong Lu ◽  
Xinghui Wu ◽  
Baojun Yu ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Nlrp3 Inflammasome ◽  
Heat Stroke ◽  
High Mobility ◽  
Molecular Probes ◽  
Toll Like Receptor 4 ◽  
Pyrin Domain ◽  
The Relationship ◽  
Related Mortality

Abstract Background: Previous studies have suggested that NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in heat stroke (HS). As a common complication in HS, thrombocytopenia has been widely considered as a good predictor of HS-related mortality. However, little is known about the relationship between inflammasome and thrombocytopenia as well as platelet activation in HS. Methods: We established a rat HS model to investigate the roles of NLRP3 inflammasome in both platelet activation and thrombocytopenia, platelet activation was reflected with Flow cytometry while thrombocytopenia was measured by platelet count. The colocalization of NLRP3 inflammasome was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) were detected using the molecular probes. Plasma HMGB1 levels were measured by ELISA.Results: Activation of the inflammasome was detected in platelet of rats in HS. Elevated ROS activated NLRP3 inflammasome in HS group could significantly induce platelet activation and thrombocytopenia. The upregulated P-selectin (CD62P ) and decreased platelet count triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) in plasma. Moreover, inhibition of HMGB1, caspase-1, NLRP3, or ROS in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4) / advanced glycation end product (RAGE) was blocked. Conclusions: This study indicated that platelets were activated by NLRP3 inflammasome through TLR4/RAGE/HMGB1 signaling pathway. The NLRP3 inflammasome might be the potential target for HS treatment.

scholarly journals Glycyrrhizin Inhibits PEDV Infection and Proinflammatory Cytokine Secretion via the HMGB1/TLR4-MAPK p38 Pathway

2020 ◽  
Vol 21 (8) ◽  
pp. 2961 ◽  
Author(s):  
Ruyi Gao ◽  
Yongshuai Zhang ◽  
Yuhui Kang ◽  
Weiyin Xu ◽  
Luyao Jiang ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
High Mobility ◽  
Cytokine Secretion ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Toll Like Receptor 4 ◽  
Diarrhea Virus ◽  
Mitogen Activated Protein ◽  
The Relationship ◽  
P38 Pathway

Our previous study showed that glycyrrhizin (GLY) inhibited porcine epidemic diarrhea virus (PEDV) infection, but the mechanisms of GLY anti-PEDV action remain unclear. In this study, we focused on the anti-PEDV and anti-proinflammatory cytokine secretion mechanisms of GLY. We found that PEDV infection had no effect on toll-like receptor 4 (TLR4) protein and mRNA levels, but that TLR4 regulated PEDV infection and the mRNA levels of proinflammatory cytokines. In addition, we demonstrated that TLR4 regulated p38 phosphorylation but not extracellular regulated protein kinases1/2 (Erk1/2) and c-Jun N-terminal kinases (JNK) phosphorylation, and that GLY inhibited p38 phosphorylation but not Erk1/2 and JNK phosphorylation. Therefore, we further explored the relationship between high mobility group box-1 (HMGB1) and p38. We demonstrated that inhibition of HMGB1 using an antibody, mutation, or knockdown decreased p38 phosphorylation. Thus, HMGB1 participated in activation of p38 through TLR4. Collectively, our data indicated that GLY inhibited PEDV infection and decreased proinflammatory cytokine secretion via the HMGB1/TLR4-mitogen-activated protein kinase (MAPK) p38 pathway.

Involvement of NLRP3 inflammasome in schizophrenia-like behaviour in young animals after maternal immune activation

2020 ◽  
Vol 32 (6) ◽  
pp. 321-327
Author(s):  
Letícia Ventura ◽  
Viviane Freiberger ◽  
Vinicius B. Thiesen ◽  
Paula Dias ◽  
Matheus L. Dutra ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Immune Activation ◽  
Nlrp3 Inflammasome ◽  
Biochemical Analysis ◽  
Future Studies ◽  
Maternal Immune Activation ◽  
Pyrin Domain ◽  
Behavioural Tests ◽  
The Relationship ◽  
The Brain

AbstractObjective:To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA).Methods:To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements.Results:It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1β levels on 7, 14 and 45 postnatal days.Conclusion:This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.

scholarly journals Leukotriene B4 Receptors are Necessary for the Stimulation of NLRP3 Inflammasome and IL-1β Synthesis in Neutrophil-Dominant Asthmatic Airway Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 535
Author(s):  
Dong-Wook Kwak ◽  
Donghwan Park ◽  
Jae-Hong Kim
Keyword(s):  
Airway Inflammation ◽  
Nlrp3 Inflammasome ◽  
Leukotriene B4 ◽  
Chronic Respiratory Diseases ◽  
Asthmatic Airway ◽  
Pyrin Domain ◽  
Dust Mite ◽  
12 Lipoxygenase ◽  
The Relationship ◽  
Stimulation Of

The stimulation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and IL-1β synthesis are associated with chronic respiratory diseases such as neutrophil-dominant severe asthma. Leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophil recruitment, and its receptors BLT1 and BLT2 have been suggested to contribute to neutrophil-dominant asthmatic airway inflammation. However, the relationship between BLT1/2 and NLRP3 in neutrophil-dominant asthmatic airway inflammation has not been previously studied. In the present study, we investigated whether BLT1/2 play any roles in stimulating the NLRP3 inflammasome and IL-1βsynthesis. The blockade of BLT1 or BLT2 clearly suppressed the stimulation of the NLRP3 inflammasome and IL-1β synthesis in house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic airway inflammation. The enzymes 5-lipoxygenase and 12-lipoxygenase, which catalyze the synthesis of BLT1/2 ligands [LTB4, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), and 12-hydroxyheptadecatreinoic acid (12-HHT)], were also critically associated with the stimulation of NLRP3 and IL-1β synthesis. Together, our results suggest that the 5-/12-LOX-BLT1/2-linked cascade are necessary for the simulation of the NLRP3 inflammasome and IL-1β synthesis, thus contributing to HDM/LPS-induced neutrophil-dominant airway inflammation.

scholarly journals Dieckol Attenuated Glucocorticoid-Induced Muscle Atrophy by Decreasing NLRP3 Inflammasome and Pyroptosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8057
Author(s):  
Seyeon Oh ◽  
Jinyoung Yang ◽  
Chulhyun Park ◽  
Kukhui Son ◽  
Kyunghee Byun
Keyword(s):  
Muscle Atrophy ◽  
Nlrp3 Inflammasome ◽  
High Mobility ◽  
Nuclear Factor Κb ◽  
High Mobility Group Protein ◽  
Cross Sectional ◽  
Downstream Signaling ◽  
Pyrin Domain ◽  
Inflammasome Component ◽  
Group Protein

Dexamethasone (Dexa), frequently used as an anti-inflammatory agent, paradoxically leads to muscle inflammation and muscle atrophy. Receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) lead to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome formation through nuclear factor-κB (NF-κB) upregulation. NLRP3 inflammasome results in pyroptosis and is associated with the Murf-1 and atrogin-1 upregulation involved in protein degradation and muscle atrophy. The effects of Ecklonia cava extract (ECE) and dieckol (DK) on attenuating Dexa-induced muscle atrophy were evaluated by decreasing NLRP3 inflammasome formation in the muscles of Dexa-treated animals. The binding of AGE or high mobility group protein 1 to RAGE or TLR4 was increased by Dexa but significantly decreased by ECE or DK. The downstream signaling pathways of RAGE (c-Jun N-terminal kinase or p38) were increased by Dexa but decreased by ECE or DK. NF-κB, downstream of RAGE or TLR4, was increased by Dexa but decreased by ECE or DK. The NLRP3 inflammasome component (NLRP3 and apoptosis-associated speck-like), cleaved caspase -1, and cleaved gasdermin D, markers of pyroptosis, were increased by Dexa but decreased by ECE and DK. Interleukin-1β/Murf-1/atrogin-1 expression was increased by Dexa but restored by ECE or DK. The mean muscle fiber cross-sectional area and grip strength were decreased by Dexa but restored by ECE or DK. In conclusion, ECE or DK attenuated Dexa-induced muscle atrophy by decreasing NLRP3 inflammasome formation and pyroptosis.

Do Extra-Platelet Sources Contribute to the Plasma Level of Thrombospondin?

1988 ◽  
Vol 59 (02) ◽  
pp. 273-276 ◽  
Author(s):  
J Dawes ◽  
D A Pratt ◽  
M S Dewar ◽  
F E Preston
Keyword(s):  
Platelet Count ◽  
Background Concentration ◽  
Serum Concentrations ◽  
Bone Marrow Depression ◽  
Serial Sampling ◽  
Control Serum ◽  
Platelet Release ◽  
Highly Correlated ◽  
The Relationship

SummaryThrombospondin, a trimeric glycoprotein contained in the platelet α-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific α-granule protein β-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma β-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Thrombotic Risk ◽  
Dose Aspirin ◽  
Gender And Age ◽  
Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Changes in Platelet Aggregability after Ovariectomy

1979 ◽  
Vol 42 (04) ◽  
pp. 1332-1339 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Takeshi Motomiya ◽  
Minoru Sonoda ◽  
Noboru Miyagawa
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Ovarian Hormones ◽  
Control Group ◽  
Platelet Aggregability ◽  
Appearance Rate ◽  
Before And After ◽  
The Difference ◽  
Induced Aggregation ◽  
Observation Period

SummaryChanges in platelets in 48 patients with uterine myoma before and after hysterectomy with and without ovariectomy were examined. Bilateral ovariectomy in 25 cases (ovariec-tomized group) and unilateral or non-ovariectomy in 23 cases (control group) were performed at the hysterectomy. Platelet count and an appearance rate of secondary aggregation decreased at one day after and increased at one week after the operation, similarly in both the ovariectomized and the control group. The appearance rate of secondary aggregation was reflected in an intensity of aggregation at 5 min after the addition of reagent to PRP. At one month after the operation, the appearance rate of secondary aggregation induced by 3 μM ADP showed a statistically significant decrease in comparison with the preoperation value (P <0.05) and the enhancement of 5-min aggregation was still observed in the control group, while ceased in the ovariectomized group. The difference between the two groups was significant (P < 0.05). There was almost no change in the speed and intensity of primary and secondary aggregation during the observation period. No significant differences in collagen-induced aggregation were noted between the two groups. The results suggest that ovarian hormones, mainly estrogen, facilitate platelet activation which is mediated by the so-called secondary aggregation.

A Simple and Rapid Method to Determine GPIIb/IIIa-Receptor Inhibitor Activity in Whole Blood

1999 ◽  
Vol 19 (03) ◽  
pp. 134-138
Author(s):  
Gitta Kühnel ◽  
A. C. Matzdorff
Keyword(s):  
Flow Cytometry ◽  
Platelet Count ◽  
Blood Sample ◽  
Platelet Activation ◽  
Whole Blood ◽  
Receptor Occupancy ◽  
Aggregate Formation ◽  
Inhibitor Activity ◽  
Receptor Inhibitor

SummaryWe studied the effect of GPIIb/IIIa-inhibitors on platelet activation with flow cytometry in vitro. Citrated whole blood was incubated with increasing concentrations of three different GPIIb/IIIa-inhibitors (c7E3, DMP728, XJ757), then thrombin or ADP were added and after 1 min the sample was fixed. Samples without c7E3 but with 0.1 U/ml thrombin had a decrease in platelet count. Samples with increasing concentrations of c7E3 had a lesser or no decrease in platelet count. The two other inhibitors (DMP 725, XJ757) gave similar results. GPIIb/IIIa-inhibitors prevent aggregate formation and more single platelets remain in the blood sample. The agonist-induced decrease in platelet count correlates closely with the concentration of the GPIIb/IIIa inhibitor and receptor occupancy. This correlation may be used as a simple measure for inhibitor activity in whole blood.

scholarly journals Anti-NLRP3 Inflammasome Natural Compounds: An Update

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 136
Author(s):  
Baolong Liu ◽  
Jiujiu Yu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Protein Complex ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Natural Compounds ◽  
Pyrin Domain ◽  
Inflammatory Protein ◽  
Wide Range ◽  
Activation Mechanisms ◽  
Stress Signals

The nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex that recognizes various danger or stress signals from pathogens, the host, and the environment, leading to activation of caspase-1 and inducing inflammatory responses. This pro-inflammatory protein complex plays critical roles in pathogenesis of a wide range of diseases including neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Therefore, intensive efforts have been devoted to understanding its activation mechanisms and to searching for its specific inhibitors. Approximately forty natural compounds with anti-NLRP3 inflammasome properties have been identified. Here, we provide an update about new natural compounds that have been identified within the last three years to inhibit the NLRP3 inflammasome and offer an overview of the underlying molecular mechanisms of their anti-NLRP3 inflammasome activities.

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