Effect of luteolin on the gene level expression of apoptosis-associated speck-like protein containing a caspase recruitment domain of NLRP3 inflammasome and NF-κB in rats subjected to experimental pancreatitis – influence of HSP70

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sadanandan Rajapriya ◽  
Arumugam Geetha
Keyword(s):  
Body Weight ◽  
Nlrp3 Inflammasome ◽  
Rank Correlation ◽  
Experimental Period ◽  
Serum Levels ◽  
Normal Diet ◽  
Experimental Pancreatitis ◽  
Caspase 1 ◽  
Spearman’S Rank Correlation ◽  
Pyrin Domain

Abstract Objectives Nod-like receptor pyrin domain containing 3 (NLRP3) is one of the well characterized inflammasome that controls the maturation of pro-inflammatory cytokines and thereby the inflammation in pancreas which could be a promising target for anti-inflammatory drugs. The present study is aimed to explore whether luteolin can target the NLRP3 inflammasome and modulate its activity through the signaling protein, HSP70 in the ethanol-cerulein model of experimental pancreatitis. Methods Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats received normal diet. Groups 3 and 4 rats received isocalorically adjusted diet containing ethanol for 5 weeks and cerulein (20 μg/kg body weight i.p., thrice weekly for the last 3 weeks of the experimental period). Additionally, group 2 and 4 rats received 2 mg/kg body weight of luteolin orally from third week. Results Luteolin co-administration decreased the serum levels of HSP70, oxidative stress markers, myeloperoxidase, GSH/GSSG and GST with concomitant downregulation in the mRNA expression of HSP70, caspase-1, ASC-NLRP3 and NF-κB. Spearman’s rank correlation test showed that serum HSP70 has positive correlation with the expression of ASC-NLRP3, caspase-1, NF-κB and 4-hydroxynonenal and negative correlation with GSH:GSSG ratio. Conclusions The modulating effect of luteolin on the expression of HSP70, NF-κB and thereby on ASC-NLRP3 complex may be claimed for its pancreato-protective activity.

Expression of caspase activation recruitment and pyrin domain levels of apoptosis-associated speck-like protein complex in the pancreas of rats subjected to experimental pancreatitis

2013 ◽  
Vol 33 (9) ◽  
pp. 940-948 ◽  
Author(s):  
R Aruna ◽  
A Geetha ◽  
P Suguna
Keyword(s):  
Mrna Expression ◽  
Messenger Rna ◽  
Experimental Period ◽  
Serum Levels ◽  
Activity Levels ◽  
Caspase Activation ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Tnf Α ◽  
Factor Α

The present study investigated the effect of rutin, a natural flavonoid, on the expression of caspase activation recruitment domain (CARD) and pyrin domain (PYD) of apoptosis-associated speck-like protein (ASC), a mediator of inflammation, in the pancreas of rats administered with ethanol (EtOH) and high-fat diet (HFD). Pancreatitis was induced in male albino Wistar rats by administering EtOH (8–12 g/kg/day) and HFD (22% fat) for 90 days. In addition, rats also received 100 mg rutin/kg body weight orally from 31st day till the experimental period. Serum levels of cytokines, interleukin 18 (IL-18) and IL-6; activity levels of caspase-1 and myeloperoxidase (MPO); messenger RNA (mRNA) expression of tumor necrosis factor α (TNF-α), caspase-1, CARD and PYD of ASC; and histological changes in pancreas were assessed. We observed a significant elevation in serum IL-18, IL-6, caspase-1 and MPO activities, mRNA expression of PYD, TNF-α and caspase-1 in the pancreas of rats administered with EtOH and HFD. Rutin administration along with EtOH and HFD significantly upregulated the mRNA expression of CARD and downregulated PYD, caspase-1, and TNF-α expressions. Rutin supplementation was also found to reduce IL-18 and IL-6 levels; and inflammatory changes in tissue architecture were evidenced by histological observations. The anti-inflammatory activity of rutin might be due to its effect on modulating the expression of ASC complex that mediates inflammation.

scholarly journals Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Bin Zheng ◽  
Shuncai Zhang ◽  
Yanlu Ying ◽  
Xinying Guo ◽  
Hengchang Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Nlrp3 Inflammasome ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Improvement Effect ◽  
Improved Performance ◽  
Inflammasome Activity ◽  
Adrenergic Receptor Agonist ◽  
Nlrp3 Activity

The abnormally high nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity is a typical characteristic of traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective α-2 adrenergic receptor agonist that inhibits the activation of NLRP3. Thus, it was hypothesized that Dex could attenuate TBI by inhibiting NLRP3 inflammasome activity in hippocampus. Rats were subjected to controlled cortical impact method to induce TBI, and treated with Dex. The effect of Dex treatment on the cognitive function, NLRP3 activity, and microglial activation in rat brain tissues was assessed. The administration of Dex improved performance of TBI rats in Morris water maze (MWM) test, which was associated with the increased neurone viability and suppressed microglia activity. Moreover, the administration of Dex inhibited the neuroinflammation in brain tissue as well as the expressions of NLRP3 and caspase-1. Additionally, Dex and NLRP3 inhibitor, BAY-11-7082 had a synergistic effect in inhibiting NLRP3/caspase-1 axis activity and improving TBI. The findings outlined in the current study indicated that the improvement effect of Dex on TBI was related to its effect on NLRP3 activity.

Abstract 404: NLR Family, Pyrin Domain-containing 3 Knockout Rescues Cardiac Dysfunction Induced by High-fat Diet Feeding

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Matthew R Peterson ◽  
Samantha Haller ◽  
Tracy Ta ◽  
Luiza Bosch ◽  
Aspen Smith ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Inflammatory Response ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Left Ventricular ◽  
Normal Diet ◽  
High Fat ◽  
Pyrin Domain

NLR family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor responsible for perpetuating an inflammatory response through production of pro-inflammatory cytokines IL-1β and IL-18. It has been implicated in the sustained inflammatory response in obesity and multiple cardiovascular disease conditions. In order to investigate NLRP3 as a potential therapeutic target in metabolic syndrome, C57BL/6 wild-type (WT) and NLRP3 knockout (NLRP3-\-) mice were fed a normal diet (ND; 12% fat chow) or a high fat diet (HFD; 45% fat chow) for 5 months. At 5 months, echocardiography and glucose tolerance tests (GTTs) were performed. Cardiac function assessed by fractional shortening (FS) was significantly impaired by HFD feeding in the WT group (0.335 HFD vs. 0.456 ND; p<0.05) but not in the NLRP3-\- (0.449 HFD vs. 0.492 ND; p>0.05). FS was higher in NLRP3-\-HFD than in WT-HFD (p<0.05). Two-dimensional analysis shows the FS difference between NLRP3-\-HFD and WT-HFD was primarily explained by the difference in left ventricular end-systolic dimension (0.2716 cm WT vs. 0.1883 cm NLRP3-\-; p<0.05). Glucose tolerance measured by area under the curve (AUC) was significantly impaired by HFD feeding for both WT (23183 ND vs. 57298 HFD; p<0.001) and NLRP3-\- (23197 ND vs. 44626 HFD; p<0.001), but significantly better in the NLRP3-\-HFD than in WT-HFD (p<0.01). HFD feeding increased fasting blood glucose (FBG) for both WT (97.7 mg . dl -1 ND vs. 164.7 mg . dl -1 HFD; p<0.01) and NLRP3-\- (80.50 mg . dl -1 ND vs. 108.8 mg . dl -1 HFD; p<0.05), but significantly less in NLRP3-\- mice (NLRP3-\- vs. WT; p<0.05). For GTTs, body weight was significantly higher in the WT than NLRP3-\- fed HFD (47.93 g vs. 36.5 g; p<0.001). Body weight explained 92% of variation in glucose tolerance (p<0.0001) and 69% of variation in fasting blood glucose (p<0.0001). WT-HFD averaged 1.31X heavier than NLRP3-\-HFD, while the AUC for the IGTT was 1.28X larger for the WT-HFD than NLRP3-\-HFD. Body weights were not significantly different between genotypes at the time of echo. The results suggest that knockout of NLRP3 may be protective against HFD induced cardiovascular dysfunction. A protective effect on glucose tolerance is not strongly supported.

Isoliquiritigenin Ameliorates Indomethacin-Induced Small Intestinal Damage by Inhibiting NOD-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation

Pharmacology ◽  
2018 ◽  
Vol 101 (5-6) ◽  
pp. 236-245 ◽  
Author(s):  
Shiro Nakamura ◽  
Toshio Watanabe ◽  
Tetsuya Tanigawa ◽  
Sunao Shimada ◽  
Yuji Nadatani ◽  
...  
Keyword(s):  
Small Intestine ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Intestinal Damage ◽  
Protein Levels ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Small Intestinal ◽  
Receptor Family

Activation of the NOD-Like Receptor Family, Pyrin Domain-Containing 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1, triggers pro-caspase-1 cleavage promoting the processing of pro-interleukin (IL)-1β into mature IL-1β, which is critical for the development of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We investigated the effects of isoliquiritigenin, a flavonoid derived from the roots of Glycyrrhiza species, on NSAID-induced small intestinal damage and the inflammasome activation. To induce enteropathy, mice were administered indomethacin by gavage with or without isoliquiritigenin pretreatment. Some mice received an intraperitoneal injection of recombinant murine IL-1β in addition to isoliquiritigenin and indomethacin. Indomethacin induced small intestinal damage and increased protein levels of cleaved caspase-1 and mature IL-1β in the small intestine. Treatment with 7.5 and 75 mg/kg isoliquiritigenin inhibited indomethacin-induced small intestinal damage by 40 and 56%, respectively. Isoliquiritigenin also inhibited the indomethacin-induced increase in cleaved caspase-1 and mature IL-1β protein levels, whereas it did not affect the mRNA expression of NLRP3, ASC, caspase-1, and IL-1β. Protection against intestinal damage in isoliquiritigenin-treated mice was completely abolished with exogenous IL-1β. NLRP3–/– and caspase-1–/– mice exhibited resistance to intestinal damage, and isoliquiritigenin treatment failed to inhibit the damage in NLRP3–/– and caspase-1–/– mice. Isoliquiritigenin prevents NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation.

A nurse as a reliable educator? Analysis of selected health behaviors of nurses

2016 ◽  
Vol 1 (1) ◽  
pp. 61-74
Author(s):  
Małgorzata Kołpa ◽  
Beata Jurkiewicz ◽  
Jolanta Nono
Keyword(s):  
Body Weight ◽  
Health Behaviors ◽  
Role Models ◽  
Healthy Lifestyle ◽  
Rank Correlation ◽  
The Body ◽  
Aerobic Activity ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Muscle Groups

Introduction: The nurse, in addition to nurture the patient should shape his awareness of a healthy lifestyle. The aim of the research was to analyze the health behaviors of nurses. Material and methods: The research participants included 100 nurses working in hospital wards. The researcher used his own questionnaire containing questions about selected lifestyle elements. The research included also the measurement of body weight and height, and the calculation of the Body Mass Index (BMI). The results were described with the use of the basic descriptive statistics, the chi2 test, Mann-Whitney U test, and the Spearman’s rank correlation coefficient. The differences were deemed significant when p<0,05. Results: Only 5.0% of nurses devoted at least 150 minutes per week to aerobic activity. More than half of the respondents (58.0%) said that on weekdays they did not perform any strength exercises for major muscle groups. According to the nurses, lack of time (65.0%) was the greatest impediment to their physical activity. A significant percentage of the respondents (40.0%) did not pay any attention to the calorific or nutritional value of their meals. As many as 30.0% of the surveyed nurses indicated that they ate irregularly, and 22.0% of them ate only 1-3 meals during the day. Excessive body weight was observed in almost half of the participants. For the majority of the nurses, their professional work was the main source of stress (46.0%). Conclusions: Despite their knowledge on healthy lifestyle, it seems that nurses do not fully implement its objectives. Therefore, the majority of them are not good role models for patients.

scholarly journals Interleukin-18 and the NLR family pyrin domain containing-3 inflammasome in adipose tissue are strongly associated with glucometabolic variables in a cohort of middle-aged men

2018 ◽  
Vol 15 (5) ◽  
pp. 458-464 ◽  
Author(s):  
Sissel Åkra ◽  
Tonje A Aksnes ◽  
Arnljot Flaa ◽  
Heidi B Eggesbø ◽  
Trine Baur Opstad ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Serum Levels ◽  
Interleukin 18 ◽  
Middle Aged ◽  
Abdominal Adipose Tissue ◽  
Genetic Expression ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Subcutaneous Adipose

Background: Previous studies have indicated an association between interleukin-18 and glucose. Interleukin-18 becomes active when cleaved by caspase-1, activated by the NLR family pyrin domain containing-3 inflammasome. Aim: To investigate associations between glucometabolic variables and serum levels of interleukin-18 and genetic expression of interleukin-18, caspase-1 and NLR family pyrin domain containing-3 in adipose tissue and circulating leukocytes, and whether these mediators are related to the amount of abdominal adipose tissue . Materials and Methods: Fasting blood samples and subcutaneous adipose tissue were collected in a cohort of 103 middle-aged men. Serum levels of interleukin-18 were determined by enzyme-linked immunosorbent assay, gene expression by real-time polymerase chain reaction and insulin sensitivity by glucose clamp. The distribution of abdominal adipose tissue, separated into superficial- and deep subcutaneous, and visceral adipose tissue, was assessed by computed tomography scan. Results: Glucometabolic variables correlated significantly to serum levels of interleukin-18, and to the expression of interleukin-18 and NLR family pyrin domain containing-3 in subcutaneous adipose tissue ( p < 0.05). Significant correlations were further observed between the amount of fat in the different compartments of abdominal adipose tissue and both serum levels of interleukin-18 and genetic expression of interleukin-18 and NLR family pyrin domain containing-3 in adipose tissue. Conclusion: The results implicate that the glucometabolic state is of importance for the inflammasome-related inflammation expressed both circulatory and genetically in subcutaneous adipose tissue, the latter highly reflected in the amount of abdominal adipose tissue.

scholarly journals Poly (I:C) and hyaluronic acid directly interact with NLRP3, resulting in the assembly of NLRP3 and ASC in a cell-free system

2017 ◽  
Vol 15 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Naoe Kaneko ◽  
Yuki Ito ◽  
Tomoyuki Iwasaki ◽  
Hiroyuki Takeda ◽  
Tatsuya Sawasaki ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Nlrp3 Inflammasome ◽  
Poly I:C ◽  
Free System ◽  
Cell Free System ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
A Cell ◽  
Homogeneous Assay ◽  
Endogenous Metabolites

In the NLR family, pyrin domain containing 3 (NLRP3) is an intracellular pattern recognition receptor that activates pro-caspase-1, leading to IL-1β and IL-18 processing and activation in a large complex called the NLRP3 inflammasome. Since various pathogens or endogenous metabolites have been reported to stimulate NLRP3 inflammasome, the interaction between NLRP3 and ASC induced by these stimulants may be an attractive drug target for NLRP3-related diseases, called inflammasomopathies. However, the endogenous ligand that directly interacts with NLRP3, leading to binding to ASC, remains unclear. Therefore, we developed a cell-free system consisting of NLRP3, ASC, and pro-caspase-1 or ASC and NLRP3 with an amplified luminescent proximity homogeneous assay (ALPHA). ALPHA signals of the interaction between NLRP3 and ASC were not enhanced following an incubation without any ligand, whereas strong ALPHA signals for the interaction between NLRP3 and ASC and between NLRP3 and pro-caspase-1 with the adaptor ASC were observed upon an incubation with poly (I:C) and hyaluronic acid (HA). Poly (I:C) and HA both directly interacted with NLRP3 within a specific concentration. These results suggest that NLRP3 directly interacts with intrinsic RNA and HA, which is followed by the activation of NLRP3 inflammasome, and the cell-free system consisting of NLRP3 and ASC, or NLRP3, ASC, and pro-caspase-1 may be a useful tool for elucidating the pathogenesis of inflammasomopathies and developing target therapeutics.

scholarly journals NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K+ efflux and Ca2+ influx

2016 ◽  
Vol 311 (1) ◽  
pp. C83-C100 ◽  
Author(s):  
Michael A. Katsnelson ◽  
Kristen M. Lozada-Soto ◽  
Hana M. Russo ◽  
Barbara A. Miller ◽  
George R. Dubyak
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Dominant Negative ◽  
Cell Physiology ◽  
Inflammasome Activation ◽  
Negative Effects ◽  
Murine Bone Marrow ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation

Nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) is a cytosolic protein that nucleates assembly of inflammasome signaling platforms, which facilitate caspase-1-mediated IL-1β release and other inflammatory responses in myeloid leukocytes. NLRP3 inflammasomes are assembled in response to multiple pathogen- or environmental stress-induced changes in basic cell physiology, including the destabilization of lysosome integrity and activation of K+-permeable channels/transporters in the plasma membrane (PM). However, the quantitative relationships between lysosome membrane permeabilization (LMP), induction of increased PM K+ permeability, and activation of NLRP3 signaling are incompletely characterized. We used Leu-Leu- O-methyl ester (LLME), a soluble lysosomotropic agent, to quantitatively track the kinetics and extent of LMP in relation to NLRP3 inflammasome signaling responses (ASC oligomerization, caspase-1 activation, IL-1β release) and PM cation fluxes in murine bone marrow-derived dendritic cells (BMDCs). Treatment of BMDCs with submillimolar (≤1 mM) LLME induced slower and partial increases in LMP that correlated with robust NLRP3 inflammasome activation and K+ efflux. In contrast, supramillimolar (≥2 mM) LLME elicited extremely rapid and complete collapse of lysosome integrity that was correlated with suppression of inflammasome signaling. Supramillimolar LLME also induced dominant negative effects on inflammasome activation by the canonical NLRP3 agonist nigericin; this inhibition correlated with an increase in NLRP3 ubiquitination. LMP elicited rapid BMDC death by both inflammasome-dependent pyroptosis and inflammasome-independent necrosis. LMP also triggered Ca2+ influx, which attenuated LLME-stimulated NLRP3 inflammasome signaling but potentiated LLME-induced necrosis. Taken together, these studies reveal a previously unappreciated signaling network that defines the coupling between LMP, changes in PM cation fluxes, cell death, and NLRP3 inflammasome activation.

Relationship between puberty in heifers and the cessation of luteal activity after nutritional restriction

1995 ◽  
Vol 61 (3) ◽  
pp. 507-510 ◽  
Author(s):  
J. A. Vizcarra ◽  
R. P. Wettemann ◽  
D. K. Bishop
Keyword(s):  
Body Weight ◽  
Correlation Coefficient ◽  
Body Condition ◽  
Body Condition Score ◽  
Rank Correlation ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Condition Score ◽  
Nutritional Restriction ◽  
The Relationship

AbstractThe relationship between puberty and the cessation of luteal activity after nutritional restriction was evaluated in 15 Angus × Hereford heifers. Heifers attained puberty at a body weight of 297 (s.e. 6) kg and a body condition score (BCS) of 5·5 (s.e. 0·1) on a scale of 1 (emaciated) to 9 (obese). After 154 (s.e. 16) days of nutritional restriction, heifers became anoestrus at a weight of 273 (s.e. 8) kg and a BCS of 3·0 (s.e. 0·2). The Spearman's rank correlation coefficient between date of-puberty and date of cessation of luteal activity was (r = –0·49; P < 0·06). This indicates that the heifers that attained puberty first were the last to cease luteal activity during nutritional restriction.

scholarly journals Emerging Role of the Inflammasome and Pyroptosis in Hypertension

2021 ◽  
Vol 22 (3) ◽  
pp. 1064
Author(s):  
Carmen De Miguel ◽  
Pablo Pelegrín ◽  
Alberto Baroja-Mazo ◽  
Santiago Cuevas
Keyword(s):  
Blood Pressure ◽  
Animal Models ◽  
Nlrp3 Inflammasome ◽  
Organ Damage ◽  
Subsequent Formation ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Inflammasomes are components of the innate immune response that have recently emerged as crucial controllers of tissue homeostasis. In particular, the nucleotide-binding domain, leucine-rich-containing (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex platform involved in the activation of caspase-1 and the maturation of interleukin (IL)-1β and IL-18, which are mainly released via pyroptosis. Pyroptosis is a caspase-1-dependent type of cell death that is mediated by the cleavage of gasdermin D and the subsequent formation of structurally stable pores in the cell membrane. Through these pores formed by gasdermin proteins cytosolic contents are released into the extracellular space and act as damage-associated molecular patterns, which are pro-inflammatory signals. Inflammation is a main contributor to the development of hypertension and it also is known to stimulate fibrosis and end-organ damage. Patients with essential hypertension and animal models of hypertension exhibit elevated levels of circulating IL-1β. Downregulation of the expression of key components of the NLRP3 inflammasome delays the development of hypertension and pharmacological inhibition of this inflammasome leads to reduced blood pressure in animal models and humans. Although the relationship between pyroptosis and hypertension is not well established yet, pyroptosis has been associated with renal and cardiovascular diseases, instances where high blood pressure is a critical risk factor. In this review, we summarize the recent literature addressing the role of pyroptosis and the inflammasome in the development of hypertension and discuss the potential use of approaches targeting this pathway as future anti-hypertensive strategies.

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