scholarly journals NLRP3 Inflammasome: A New Pharmacological Target for Reducing Testicular Damage Associated with Varicocele

2021 ◽  
Vol 22 (3) ◽  
pp. 1319
Author(s):  
Pietro Antonuccio ◽  
Antonio Girolamo Micali ◽  
Carmelo Romeo ◽  
Jose Freni ◽  
Giovanna Vermiglio ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Male Rats ◽  
Sham Operation ◽  
Testicular Damage ◽  
Cell Numbers ◽  
Testosterone Levels ◽  
Caspase 1 ◽  
Ultrastructural Damage ◽  
Pharmacological Target

Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1β and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1β expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.

Involvement of physiological prolactin levels in growth and prolactin receptor content of prostate glands and testes in developing male rats

1992 ◽  
Vol 132 (3) ◽  
pp. 449-459 ◽  
Author(s):  
B. Pérez-Villamil ◽  
E. Bordiú ◽  
M. Puente-Cueva
Keyword(s):  
Body Weight ◽  
Male Rats ◽  
Ventral Prostate ◽  
Serum Prolactin ◽  
Plasma Prolactin ◽  
Stages Of Development ◽  
Continuous Increase ◽  
Testosterone Levels ◽  
Testicular Weight

ABSTRACT We have investigated the role of physiological prolactin levels in the development of prepubertal male rats. Prolactin GH and testosterone levels, as well as body, ventral prostate and testicular weight, have been analysed in both control and bromocriptine-treated rats between 21 and 60 days of life. Furthermore the role of prolactin in the regulation of its own receptors has also been studied during the same period. In control rats, prolactin levels showed a prepubertal peak of secretion at 25 days of age. At this time GH and testosterone levels were low and did not show any significant variation. After this age, prolactin levels increased more gradually; determinations of GH showed great variation with low levels in most of the rats and very high values in the other animals; testosterone levels remained low until day 35 after which they increased. Simultaneously with the serum prolactin peak on day 25, a decrease in prolactin-binding capacity of ventral prostate glands, was observed and a maximum rate of body, prostate and testicular weight gain was obtained. Furthermore, in rats with pharmacologically suppressed serum prolactin levels (lower than 1 μg/l), prolactin binding to prostate glands as well as the weight of body, ventral prostate and testes were lower than in control animals. When results were expressed in mg prostate or testes/g body weight, testes from 25-day-old treated rats weighed significantly less than controls. The later stages of development, from days 25 to 60, were characterized by an initial decline in serum prolactin levels at 29 days of age which was followed by a continuous increase until adult values were reached. During this period, prostatic prolactin receptors which were at their lowest value at 33 days of age showed a gradual rise parallel with the observed increase in plasma prolactin levels. When testicular tissue was analysed, no changes in prolactin-binding sites caused by sexual maturation were observed. The present results indicate that physiological prolactin secretion has a specific effect on the normal increase in the prostate, testes and body weight and clearly is also implicated in the regulation of its prostatic receptors at the earlier stages of development. Journal of Endocrinology (1992) 132, 449–459

scholarly journals The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification

Inflammation ◽  
2020 ◽  
Author(s):  
Chenyang Yu ◽  
Caihua Zhang ◽  
Zhihui Kuang ◽  
Qiang Zheng
Keyword(s):  
Vascular Calcification ◽  
Nlrp3 Inflammasome ◽  
Periodontal Diseases ◽  
Bone Destruction ◽  
Bone Diseases ◽  
Sterile Inflammation ◽  
Inflammatory Factors ◽  
Bone Homeostasis ◽  
Caspase 1

Abstract Continuous stimulation of inflammation is harmful to tissues of an organism. Inflammatory mediators not only have an effect on metabolic and inflammatory bone diseases but also have an adverse effect on certain genetic and periodontal diseases associated with bone destruction. Inflammatory factors promote vascular calcification in various diseases. Vascular calcification is a pathological process similar to bone development, and vascular diseases play an important role in the loss of bone homeostasis. The NLRP3 inflammasome is an essential component of the natural immune system. It can recognize pathogen-related molecular patterns or host-derived dangerous signaling molecules, recruit, and activate the pro-inflammatory protease caspase-1. Activated caspase-1 cleaves the precursors of IL-1β and IL-18 to produce corresponding mature cytokines or recognizes and cleaves GSDMD to mediate cell pyroptosis. In this review, we discuss the role of NLRP3 inflammasome in bone diseases and vascular calcification caused by sterile or non-sterile inflammation and explore potential treatments to prevent bone loss.

scholarly journals Intraventricular T3 reverses chronic restraint stress-induced depressive-like behaviors: Inhibition of NF-κB/ NLRP3 inflammasome pathway in the hippocampus

2021 ◽  
Author(s):  
Tahmineh Mokhtari ◽  
AymanEl-Meghawry El-Kenawy ◽  
Li Hu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Restraint Stress ◽  
Male Rats ◽  
Control Group ◽  
Therapeutic Effects ◽  
Chronic Restraint Stress ◽  
Model Group ◽  
Nissl Staining ◽  
Caspase 1 ◽  
Ca1 Region

Abstract In this study, the effects of triiodothyronine (T3) were evaluated on the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex formation in the rat's hippocampus with restraint stress-induced depressive-like behaviors.Thirty-six Wistar male rats were randomly allocated to following groups: Control, Model, and Model + T3. In the Model or Model+T3 group, a single dose of PBS or T3 was administered into the lateral ventricle. Depressive-like behaviors were induced by chronic restraint stress. The forced swimming (FST), tail suspension (TST), and open field (OFT) tests were used to investigate the depression. The rats were sacrificed, and brain tissues were stored for molecular and pathological evaluations. Chronic stress increased the immobility of rats in the Model group according to FST, TST, and OFT (P < 0.05). T3 significantly improved depressive-like behaviors (P < 0.05). The gene expression and protein level of hippocampal nuclear factor kappa B (NF-κB), NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 significantly increased in the Model group compared to the control group (P < 0.05). The reduced hippocampal levels of NF-κB, NLRP3, ASC, and Caspase-1 were observed in the T3 group compared to the Model group (P < 0.05). The Nissl staining of the CA1 region showed an increased number of dark neurons (P < 0.05) and reduced pyramidal layer thickness (P < 0.05) in the Model group. These histopathological alterations were changed by T3 administration compared to the Model group (P < 0.05). The findings confirmed the therapeutic effects of intraventricularly T3 on depressive-like behaviors induced by restraint stress via surviving pyramidal neurons of the CA1 region and inhibition of NF-κB/NLRP3 inflammasome pathway.

scholarly journals The Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Shizhen Zhao ◽  
Xiaotian Li ◽  
jie Wang ◽  
Honggang Wang
Keyword(s):  
Nervous System ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Hypoperfusion ◽  
Receptor Protein ◽  
Future Research ◽  
Nervous System Diseases ◽  
Caspase 1

Autophagy is a stable self-sustaining process in eukaryotic cells. In this process, pathogens, abnormal proteins, and organelles are encapsulated by a bilayer membrane to form autophagosomes, which are then transferred to lysosomes for degradation. Autophagy is involved in many physiological and pathological processes. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, containing NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1, can activate caspase-1 to induce pyroptosis and lead to the maturation and secretion of interleukin-1 β (IL-1 β) and IL-18. NLRP3 inflammasome is related to many diseases. In recent years, autophagy has been reported to play a vital role by regulating the NLRP3 inflammasome in inflammatory nervous system diseases. However, the related mechanisms are not completely clarified. In this review, we sum up recent research about the role of the effects of autophagy on NLRP3 inflammasome in Alzheimer’s disease, chronic cerebral hypoperfusion, Parkinson’s disease, depression, cerebral ischemia/reperfusion injury, early brain injury after subarachnoid hemorrhage, and experimental autoimmune encephalomyelitis and analyzed the related mechanism to provide theoretical reference for the future research of inflammatory neurological diseases.

Role of NLRP3-Inflammasome/Caspase-1/Galectin-3 Pathway on Atrial Remodeling in Diabetic Rabbits

2020 ◽  
Vol 13 (5) ◽  
pp. 731-740 ◽  
Author(s):  
Xiaohan Wu ◽  
Yang Liu ◽  
Daimiao Tu ◽  
Xianjian Liu ◽  
Shulin Niu ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Atrial Remodeling ◽  
Caspase 1 ◽  
Galectin 3 ◽  
Diabetic Rabbits

Abstract 127: Txnip-Mediated NLRP3 Inflammasome Activation as a Novel Mechanism of Myocardial Ischemia-Reperfusion Injury

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Yi Liu ◽  
Lijian Zhang ◽  
Yan Qu ◽  
Chao Gao ◽  
Jingyi Liu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Myocardial Ischemia Reperfusion

As an inhibitor of the antioxidant thioredoxin, thioredoxin-interacting protein (Txnip) is linked to insulin resistance. NLRP3 inflammasome, a major regulator of innate immunity, has been reported to be activated by Txnip, thus contributing to the pathogenesis of type 2 diabetes mellitus. However, the role of Txnip and its NLRP3 inflammasome activation in the myocardial ischemia/reperfusion (MI/R) injury has not been previously investigated. C57BL/6J mice were subjected to 30 min of ischemia and 3 or 24 hrs of reperfusion. The ischemic heart exhibited increased Txnip and NLRP3 expressions, increased interaction between Txnip and NLRP3 (by immunoprecipitation, 1.8-fold increase over sham), and increased IL-1β, IL-18 and caspase-1 expressions (%increase: 80%, 77% and 110%, respectively) (n=8, all P <0.05). Compared with vehicle group, those mice either receiving intramyocardial small-interfering RNA (siRNA) injection to specifically knockdown the myocardial NLRP3 or intraperitoneal injection of the inflammasome inhibitor (BAY 11-7082) exhibited significantly improved cardiac function (by 28% and 25%), decreased the infarct size (by 40% and 38%), and decreased the cardiomyocytes apoptosis (all P <0.05). NLRP3 knockdown or inflammasome inhibitor also decreased the inflammatory cells infiltration (macrophages and neutrophils) and cytokines (TNF-α, INF-γ and IL-6) production (all P <0.05). To elucidate the role of Txnip in the NLRP3 activation in MI/R, intramyocardial injection of Txnip siRNA was performed to specifically knockdown the myocardial Txnip expression. Compared with vehicle, the Txnip knockdown significantly decreased Txnip/NLRP3 interaction and NLRP3activation as evidenced by lower expressions of IL-1β and caspase-1, decreased inflammatory cells infiltration and cytokines expressions, and consequently decreased the myocardial infarct size and increased the heart function (all P <0.05). Collectively, we demonstrated for the first time that Txnip mediatedNLRP3 inflammasome activation is a novel mechanism of MI/R injury. Interventions targeted to blocking the activation of NLRP3 by inhibiting Txnip may have therapeutic potential for preventing MI/R injury.

Dual Targeting of Autophagy and NF-κB Pathway by PPARγ Contributes to the Inhibitory Effect of Demethoxycurcumin on NLRP3 Inflammasome Priming

2021 ◽  
Vol 14 ◽  
Author(s):  
Jing Tang ◽  
Xiaoxue Tan ◽  
Xiangmi Huang ◽  
Jie Zhang ◽  
Liang Chen ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Nuclear Translocation ◽  
Inhibitory Effect ◽  
Caspase 1 ◽  
Dual Targeting ◽  
Transmission Electron ◽  
Subsequent Activation ◽  
Natural Derivative ◽  
Pparγ Expression

Background: Demethoxycurcumin (DMC), a natural derivative of curcumin, has anti-inflammatory activities. However, the mechanism has not been fully elucidated. Objective: The aim of the current study was to investigate the role of DMC on NLRP3 inflammasome priming. Methods: Protein expression was quantified by western blotting. Inflammatory cytokines were measured by ELISA. Autophagosomes were evaluated by transmission electron microscopy. Results: DMC inhibited LPS-stimulated NLRP3, pro-caspase-1, and pro-IL-1β expression. Meanwhile, DMC diminished NLRP3-dependent IL-1β maturation, caspase-1 activation, IL-1β and IL-18 production caused by LPS plus ATP. Moreover, DMC induced autophagy and autophagy inhibitor 3-MA abrogated the role of DMC on NLRP3 inflammasome priming and subsequent activation. DMC also inhibited LPS-stimulated phosphorylation and nuclear translocation of p65 NF-κB. Additionally, DMC significantly increased the PPARγ expression and the effects of DMC in NF-κB inhibition, autophagy, and NLRP3 inflammasome priming were abrogated by specific PPARγ antagonist T0070907. Conclusion: The evidence presented here has confirmed that DMC increases PPARγ expression, resulting in autophagy and NF-κB inhibition, and subsequently inhibits LPS-induced NLRP3 inflammasome priming and subsequent activation.

NLRP3 inflammasome activation contributes to aldosterone-induced podocyte injury

2017 ◽  
Vol 312 (4) ◽  
pp. F556-F564 ◽  
Author(s):  
Mi Bai ◽  
Ying Chen ◽  
Min Zhao ◽  
Yue Zhang ◽  
John Ci-Jiang He ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Renal Tubules ◽  
Mineralocorticoid Receptor Antagonist ◽  
Podocyte Injury ◽  
Nlrp3 Gene ◽  
Caspase 1 ◽  
Focal Segmental Glomerular Sclerosis ◽  
Nlrp3 Inflammasome Activation

Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1, and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by the mineralocorticoid receptor antagonist eplerenone or the antioxidant N-acetylcysteine. Silencing NLRP3 by a siRNA approach strikingly attenuated Aldo-induced podocyte apoptosis and nephrin protein downregulation in line with the blockade of caspase-1 and IL-18. In vivo, since day 5 of Aldo infusion, NLRP3 inflammasome activation and podocyte injury evidenced by nephrin reduction occurred concurrently. More importantly, immunofluorescence analysis showed a significant induction of NLRP3 in podocytes of glomeruli following Aldo infusion. In the mice with NLRP3 gene deletion, Aldo-induced downregulation of nephrin and podocin, podocyte foot processes, and albuminuria was remarkably improved, indicating an amelioration of podocyte injury. Finally, we observed a striking induction of NLRP3 in glomeruli and renal tubules in line with an enhanced urinary IL-18 output in nephrotic syndrome patients with minimal change disease or focal segmental glomerular sclerosis. Together, these results demonstrated an important role of NLRP3 inflammasome in mediating the podocyte injury induced by Aldo.

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