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1.
Arq. bras. oftalmol ; 84(1): 67-73, Jan.-Feb. 2021. graf
Article in English | LILACS | ID: biblio-1153097

ABSTRACT

ABSTRACT Purpose: Diabetic retinopathy is currently considered a chronic inflammatory disease involving NOD-like receptor family pyrin domain containing 3 inflammasome activation and retinal microglial pyroptosis. In this study, we aimed to investigate whether NOD-like receptor family pyrin domain containing 3 inflammasome signaling induces pyroptotic death of retinal microglia under high-glucose conditions. Methods: Retinal microglia were stimulated by high glucose levels for 24 h. Cell viability, lactate dehydrogenase release, and caspase-1 activity were detected in vitro. The expression of pro-inflammatory cytokine (interleukin-1β, activated microglia marker ionized calcium-binding adapter molecule-1), NOD-like receptor family pyrin domain containing 3, cleaved caspase-1, and cleaved gasdermin D were examined. Subsequently, retinal microglia were pretreated with the inhibitors of NOD-like receptor family pyrin domain containing 3 inflammasome signaling prior to stimulation with high glucose, and their molecular and functional changes were evaluated. Results: High-glucose (25, 50, or 100 mM) stimulation decreased cell viability, but enhanced lactate dehydrogenase release and caspase-1 activity in a dose-dependent manner. Moreover, high glucose upregulated the protein expression of interleukin-1β, ionized calcium-binding adapter molecule-1, NOD-like receptor family pyrin domain containing 3, cleaved caspase-1, and cleaved gasdermin D. However, pretreatment with the inhibitors of NOD-like receptor family pyrin domain containing 3 inflammasome signaling inhibited high glucose (25 mM)-induced cytotoxicity, NOD-like receptor family pyrin domain containing 3 inflammasome activation, and pyroptosis of retinal microglia. Conclusions: NOD-like receptor family pyrin domain containing 3 inflammasome signaling may modulate retinal microglia-related inflammation and pyroptosis under high-glucose conditions.


RESUMO Objetivo: Atualmente, a retinopatia diabética é considerada uma doença inflamatória crônica envolvendo a ativação de inflamassomas NLRP3 e piroptose da micróglia da retina. Neste estudo, objetivamos investigar se a sinalização de inflamassomas NLRP3 induz a morte da micróglia da retina sob condições de alta glicose. Métodos: A micróglia da retina foi estimulada por altos níveis de glicose durante 24 horas. A viabilidade celular, a liberação de LDH e a atividade da caspase1 foram analisadas in vitro. Avaliou-se a expressão de citocina pró-inflamatória (IL1β), de marcador de micróglia ativado (Iba1), de NLRP3, de caspase1 clivada e de GSDMD clivada. Subsequentemente, a micróglia da retina foi pré-tratada com inibidores da sinalização de inflamassomas NLRP3 antes da estimulação com altos níveis de glicose e suas alterações moleculares e funcionais foram avaliadas. Resultados: A estimulação com altos níveis de glicose (25 mM, 50 mM ou 100 mM) diminuiu a viabilidade celular, mas aumentou a liberação de LDH e a atividade da caspase1 de forma dependente da dose. Além disso, os altos níveis de glicose aumentaram a expressão das proteínas IL1β, Iba1, NLRP3, caspase1 clivada e GSDMD clivada. No entanto, o pré-tratamento com inibidores da sinalização de inflamassomas NLRP3 e a posterior estimulação com altos níveis de glicose (25 mM) induziu citotoxicidade, a ativação de inflamassomas NLRP3 e a piroptose da micróglia da retina. Conclusão: A sinalização de inflamassomas NLRP3 pode modular a inflamação e a piroptose da micróglia da retina na presença de altos níveis de glicose.


Subject(s)
Humans , Inflammasomes , Pyroptosis , Microglia , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein , Glucose
2.
Article in Chinese | WPRIM | ID: wpr-888152

ABSTRACT

In this study, we investigated the mechanism of crude extract of Psammosilene tunicoides(CEPT) in the treatment of rheumatoid arthritis(RA) based on the Nod-like receptor protein 3(NLRP3) inflammasome. The collagen-induced arthritis(CIA) mouse model was established. On day 32 after the primary immunization, according to the arthritis score, the mice were randomly divided into model group, positive control(methotrexate) group, low-and high-dose CEPT groups, and normal group, with 10 mice in each group. According to the administration dose of each group, the mice were continuously administered for 21 days. Every four days during the administration, the paw edema degree, arthritis score, and spleen index of the mice were measured; histopathological examination was performed for the ankles of the mice; the contents of IL-1β and IL-18 in the serum were determined; the protein expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a CARD(ASC), as well as the mRNA expression levels of NLRP3 and caspase-1 in the ankle joints of the mice were detected. The results showed that compared with those in the model group, the mice in the positive control group and CEPT groups had significantly decreased the contents of IL-1β and IL-18 in the serum and spleen index(P<0.01), significantly lowered arthritis score and degree of paw edema(P<0.01), alleviated arthritic infiltration of the knee, and down-regulated protein and mRNA levels of NLRP3, ASC, and caspase-1 in the ankle joint(P<0.01). These results suggest that P. tunicoides may reduce the paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3. This study provides a basis for the study of immune regulation of P. tunicoides in RA.


Subject(s)
Animals , Arthritis, Experimental/genetics , Arthritis, Rheumatoid/genetics , Caspase 1/genetics , Inflammasomes/genetics , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/genetics
3.
Article in Chinese | WPRIM | ID: wpr-888149

ABSTRACT

This study investigated the mechanism of improving impaired glucose tolerance(IGT) of rats by Huanglian Wendan Decoction from the perspective of the skeletal muscle Nod-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/interleukin-1β(IL-1β), interleukin-18(IL-18) pathway. Healthy male SD rats were fed with the diet containing 45% fat for 20 weeks, accompanied by a high-temperature and high-humidity environment and an inactive lifestyle, for the establishment of the IGT rat model. The rats were divided into the blank control group, model control group, metformin hydrochloride group(positive drug group, 0.05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group(7.8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks, the obesity and glycemic indexes of all the rats were measured. The fasting serum insulin(FINS) level was determined by ELISA, with the insulin sensitivity index(ISI) and insulin resistance index(IRI) calculated. The mRNA and protein expression le-vels of nuclear factor kappaB(NF-κB), NLRP3, caspase-1, IL-1β and IL-18 in skeletal muscle tissue were detected by real-time polymerase chain reaction(PCR), Western blot and immunofluorescence. Compared with the blank control group, the model control group witnessed significantly increased mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18. As revealed by the comparison with the model control group, Huanglian Wendan Decoction could effectively regulate the obesity status, reduce body weight, correct the abnormal levels of 2-hour plasma glucose(2 hPG), insulin resistance index(IRI), insulin sensitivity index(ISI), and lower the mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18 in the skeletal muscle tissue of IGT rats. Combined with previous studies, the above results showed that the occurrence and development of IGT was closely related to inflammatory response and the classic pyroptosis pathway in skeletal muscle, such as NLRP3/caspase-1/IL-1β, IL-18. It is inferred that the mechanism of Huanglian Wendan Decoction was to alleviate insulin resistance(IR) and then reverse the course of IGT lies in the regulation of the abnormal insulin receptor signaling pathway based on the NLRP3 inflammasome pathway.


Subject(s)
Animals , Caspase 1/genetics , Drugs, Chinese Herbal , Glucose Intolerance , Interleukin-18/genetics , Interleukin-1beta , Male , Muscle, Skeletal , NF-kappa B/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Rats , Rats, Sprague-Dawley
4.
Article in Chinese | WPRIM | ID: wpr-887989

ABSTRACT

To study the mechanism of polysaccharides from seeds of Vaccaria segetalis( PSV) in the treatment of bacterial cystitis through the NLRP3 inflammasome pathway. The rat model of urinary tract infection was used and treated with PSV,and the urine and bladders were collected. The level of interleukin-10( IL-10) in rat urine was detected by enzyme linked immunosorbent assay( ELISA). Western blot and immunofluorescence staining were used to detect the expressions of sonic hedgehog( SHH) and NLRP3 inflammasome [NOD-like receptor thermoprotein domain 3( NLRP3),apoptosis associated speck like protein( ASC) and pro-caspase-1]. The expression of Toll-like receptor pathway was detected by RT-PCR. The death of 5637 cells induced by uropathogenic Escherichia coli( UPEC) and lactate dehydrogenase( LDH) release were evaluated using live/dead staining. The results showed that in the rat bladder,the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors were significantly up-regulated,and NLRP3 inflammasomes were significantly activated by UPEC infection. The administration with PSV could significantly increase the concentration of IL-10 in urine,inhibit the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors in bladder,and inhibit the activation of NLRP3 inflammasomes. A large number of 5637 cells were dead after UPEC infection and caused LDH production. PSV could significantly inhibit the death of 5637 cells and the release of LDH. In conclusion,PSV could inhibit the expression and activation of NLRP3 inflammasomes by inhibiting the Toll-like receptor pathway,thereby mitigating the bladder injury.


Subject(s)
Animals , Hedgehog Proteins , Inflammasomes/genetics , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Polysaccharides/pharmacology , Rats , Seeds , Urinary Bladder , Urinary Tract Infections/drug therapy , Vaccaria
5.
Acta Physiologica Sinica ; (6): 329-341, 2021.
Article in Chinese | WPRIM | ID: wpr-878261

ABSTRACT

Pyroptosis is a form of programmed cell death which is closely related to the inflammatory response, mediated by Gasdermin protein and depends on the activity of cysteine aspartate specific protease (caspase). Pyroptosis is typically characterized by swelling and rupture of cell membrane, release of proinflammatory factors and cell contents from the plasma membrane to the extracellular environment, which aggravates inflammatory response. During the inflammatory response, NLRP3, caspase, Gasdermin D (GSDMD) and IL-1β play important roles in the occurrence and development of cardiovascular diseases. In this review, we focus on the role of pyroptosis in cardiovascular diseases including atherosclerosis, coronary heart disease, myocardial infarction, diabetic cardiomyopathy, pressure overload-induced ventricular remodeling and cardiac hypertrophy, myocarditis, arrhythmia and so on, and summarize the potential treatment targeting pyroptosis. It will provide the basis for prevention and treatment of clinical cardiovascular diseases.


Subject(s)
Apoptosis , Cardiovascular Diseases , Caspases , Humans , NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis
6.
Article in Chinese | WPRIM | ID: wpr-880827

ABSTRACT

OBJECTIVE@#To investigate the role of NDUFA13 inactivation in the pathogenesis of spontaneous hepatitis in mice and explore the possible mechanisms.@*METHODS@#Hepatocyte-specific NDUFA13 knockout (NDUFA13@*RESULTS@#Liver-specific NDUFA13 heterozygous knockout mice were successfully constructed as verified by PCR results. HE staining revealed severe liver damage in both 4- week-old and 2-year-old NDUFA13@*CONCLUSIONS@#Hepatocytes-specific NDUFA13 ablation can trigger spontaneous hepatitis in mice possibly mediated by the activation of ROS/NF-κB/NLRP3 signaling.


Subject(s)
Animals , Hepatitis , Inflammasomes , Mice , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Signal Transduction
7.
Journal of Experimental Hematology ; (6): 1566-1569, 2021.
Article in Chinese | WPRIM | ID: wpr-922296

ABSTRACT

OBJECTIVE@#To clarify the significance of inflammasome NLRP3 in children with immune thrombocytopenia (ITP) by detecting its changes before and after treatment.@*METHODS@#Twenty children with ITP diagnosed and treated in Xuzhou Children's Hospital were enrolled as observation group, and 10 healthy children as control group. The mRNA levels of NLRP3, ASC, and Caspase-1 were measured by real-time quantitative PCR (RT-qPCR), the serum levels of IL-18, IL-1β, and high mobility group protein B1 (HMGB1) were detected by ELISA, and the protein level of NLRP3 was detected by Western blot.@*RESULTS@#In newly diagnosed ITP children, the serum levels of IL-18, IL-1β and HMGB1 significantly decreased after treatment (P<0.05). After treatment, NLRP3, ASC, and Caspase-1 mRNA levels in peripheral blood mononuclear cells were significantly lower than those before treatment (P<0.05). NLRP3 protein expression decreased significantly after treatment.@*CONCLUSION@#Expression of NLRP3 inflammasome and downstream inflammatory factors are decrease after treatment in children with ITP, which may be used as effective prognostic markers.


Subject(s)
Child , HMGB1 Protein , Humans , Inflammasomes , Leukocytes, Mononuclear , NLR Family, Pyrin Domain-Containing 3 Protein , Purpura, Thrombocytopenic, Idiopathic
8.
Article in Chinese | WPRIM | ID: wpr-921747

ABSTRACT

This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.


Subject(s)
AMP-Activated Protein Kinases/genetics , Animals , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , Mice , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts , Rehmannia , Signal Transduction , Streptozocin
9.
Article in Chinese | WPRIM | ID: wpr-921664

ABSTRACT

Pyroptosis is a pro-inflammatory programmed cell death, and its role in cardiac inflammatory response has become a hot topic. The activation of nucleotide binding oligomerization domain like receptor protein 3(NLRP3) inflammasome is an important mechanism for pyroptosis induced by cysteinyl aspartate specific proteinase 1(caspase-1). The existing studies have shown that cardiomyocyte pyroptosis participates in the pathogenesis of different cardiovascular diseases and the NLRP3 inflammasome-mediated cardiomyocyte pyroptosis has been most widely studied. Also, the intervention in NLRP3 inflammasome activation and cardiomyocyte pyroptosis contributes to ameliorating myocardial injury, which may be the main mechanism of many traditional Chinese medicines in exerting the cardio-protective effects. Therefore, this paper reviewed the studies on cardiomyocyte pyroptosis mediated by NLRP3 inflammasome and put forward the importance of exploring traditional Chinese medicine intervention in the activation of NLRP3 inflammasome.


Subject(s)
Inflammasomes , Medicine, Chinese Traditional , Myocytes, Cardiac , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Pyroptosis
10.
Article in Chinese | WPRIM | ID: wpr-921648

ABSTRACT

The rats were exposed to chronic unpredictable mild stress(CUMS) and kept in separate cages for inducing depressive disorder, which was judged by behavioral indicators. The number and morphology of neurons in hippocampal CA3 area and prefrontal cortex were observed by hematoxylin-eosin(HE) staining. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), norepinephrine(NE), glutamic acid(GLU), interleukin-1β(IL-1β), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(RT-PCR) and Western blot were conducted to determine the mRNA and protein expression levels of related molecules in NLRP3 pathway. The results showed that compared with the model group, acidic polysaccharides from Poria at the low-, medium-, and high-doses(0.1, 0.3 and 0.5 g·kg~(-1)·d~(-1)) all improved the depression-like behavior of rats, increased the number of neurons and the levels of BDNF, 5-HT, 5-HIAA, DA, and NE in the hippocampus, and reduced GLU and serum IL-1β, IL-18, and TNF-α levels. The mRNA expression levels of ASC, caspase-1, IL-1β, and IL-18 and the protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in each medication group were down-regulated, whereas the protein expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18 were up-regulated. All these have indicated that acidic polysaccharides from Poria exerted the antidepressant effect possibly by regulating neurotransmitters and NLRP3 inflammasome signaling pathway.


Subject(s)
Animals , Antidepressive Agents , Depression/drug therapy , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Neurotransmitter Agents , Polysaccharides/pharmacology , Poria , Rats
11.
Article in Chinese | WPRIM | ID: wpr-921539

ABSTRACT

Alzheimer's disease(AD)is a chronic neurodegenerative disease whose cause remains unclear.The β-amyloid plaques in the brain are one of the major pathological features of AD.However,the drugs targeting extracellular β-amyloid plaques have failed to cure the disease.Innate immunity and neuroinflammation play a role in the pathogenesis and progression of AD.As the macrophages existing in the central nervous system,microglia are related with extracellular β-amyloid deposition,intracellular neurofibrillary tangle formation,and neuron injury.Accumulating evidence demonstrates that the activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3)inflammasome in microglia plays a role in AD,suggesting new therapeutic target for AD in this signaling pathway.This article reviewed the studies about the activation and regulation of NLRP3 inflammasome in the pathogenesis and progression of AD as well as the development of AD therapies targeting this pathway,aiming to provide reference for further studies in this field.


Subject(s)
Alzheimer Disease , Humans , Inflammasomes , Microglia , NLR Family, Pyrin Domain-Containing 3 Protein , Neurodegenerative Diseases , Nucleotides , Pyrin Domain
12.
Journal of Integrative Medicine ; (12): 428-438, 2021.
Article in English | WPRIM | ID: wpr-888771

ABSTRACT

OBJECTIVE@#High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assessed the anti-NAFLD effect of SLBZP in vivo.@*METHODS@#Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array.@*RESULTS@#SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues.@*CONCLUSION@#SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1β release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases.


Subject(s)
Animals , Liver , NLR Family, Pyrin Domain-Containing 3 Protein , Non-alcoholic Fatty Liver Disease/drug therapy , Powders , Rats , Toll-Like Receptor 4 , X-Ray Microtomography
13.
Frontiers of Medicine ; (4): 594-607, 2021.
Article in English | WPRIM | ID: wpr-888746

ABSTRACT

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.


Subject(s)
Adenosine Triphosphate , Animals , Chemical and Drug Induced Liver Injury/etiology , Flavonoids , Humans , Inflammasomes , Mice , NLR Family, Pyrin Domain-Containing 3 Protein , Nigericin
14.
Article in Chinese | WPRIM | ID: wpr-879053

ABSTRACT

To study the effect and mechanism of extract of Quzhou Aurantii Fructus(QAF) on liver inflammation in CCl_4-induced liver fibrosis mice. Totally 60 C57 BL/6 male mice were randomly divided into control group(distilled water, oral), model group(distilled water, oral), colchicines group(Col, colchicines 2 mg·kg~(-1)·d~(-1), oral), low-dose QAF group(QAF-L, QAF 100 mg·kg~(-1)·d~(-1), oral) and high-dose QAF group(QAF-H, QAF 300 mg·kg~(-1)·d~(-1), oral) by random number table method. The model group and each administration group were injected with carbon tetrachloride(CCl_4) 1 mL·kg~(-1)(CCl_4-olive oil 1∶4), twice a week, totally 6 weeks. After the last administration, the mice were sacrificed, and serum and liver tissue were collected. Serum ALT and AST levels were measured in each group to observe the liver function of mice. The pathological changes and inflammatory cell infiltration in liver were observed by HE staining and F4/80 immunohistochemical staining. The mRNA expressions of TNF-α, IL-18 and IL-1β were detected by RT-PCR. The protein expressions of IκBα, p-IKKα/β, p-p65, NLRP3, caspase-1 and cleaved caspase-1 were analyzed by Western blot. The results showed that QAF significantly reduced serum ALT and AST levels, and alleviated the degree of liver damage.The results of immunohistochemistry showed that QAF significantly reduced liver inflammatory cell infiltration in liver fibrosis mice. The results of RT-PCR and Western blot showed that QAF significantly inhibited mRNA expressions of TNF-α, IL-18 and IL-1β in liver of fibrosis mice. QAF also suppressed the degradation of IκBα protein and reduced p-IKKα/β, p-p65, NLRP3 and cleaved caspase-1 protein expressions. In conclusion, QAF improves CCl_4-induced liver fibrosis in mice. The mechanism may be related to the inhibition of NF-κB/NLRP3 inflammasome-mediated inflammation signaling pathway.


Subject(s)
Animals , Inflammasomes/genetics , Inflammation , Liver/pathology , Liver Cirrhosis/genetics , Male , Mice , NF-kappa B/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Plant Extracts
15.
Article in Chinese | WPRIM | ID: wpr-879021

ABSTRACT

To explore the effect of Huangqin Decoction on ulcerative colitis(UC) pyroptosis, and to explain the mechanism of pyroptosis based on NOD-like receptor thermoprotein domain 3(NLRP3)/cysteine proteinase 1(caspase-1) pathway. The animal model of UC induced with 3% dextran sodium sulfate(DSS) was established. The experimental animals were divided into control group, model group, low-dose(4.55 g·kg~(-1)), medium-dose(9.1 g·kg~(-1)) and high-dose(18.2 g·kg~(-1)) Huangqin Decoction groups and salazosulfapyridine group(0.45 g·kg~(-1)). While modeling, intragastric administration was given for 7 consecutive days. On the 8 th day, the mice were euthanized, the colon length was collected, and the histopathological changes were observed by HE staining. The content of interleukin-18(IL-18) was observed by ELISA. The content of lactatedehydrogenase(LDH)was determined by microplate method. TUNEL assay kit was used to detect the cell death. The immunohistochemical staining was used to detect the expressions of NLRP3 and apoptosis-associated speck-like protein containing a CARD(ASC). Western blot was used to detect the expressions of interleukin-1β(IL-1β), caspase-1 and gasdermin D(GSDMD).The experimental study showed that compared with normal group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were significantly increased(P<0.05). Compared with model control group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were decreased, and these results were more significant in high-dose groups(P<0.05). The results of HE staining showed that Huangqin Decoction could improve the pathological changes of colon. Huangqin Decoction could inhibit UC cell pyroptosis, and the mechanism may be closely related to NLRP3/caspase-1 signaling pathway.


Subject(s)
Animals , Caspase 1/genetics , Colitis, Ulcerative/drug therapy , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Pyroptosis , Scutellaria baicalensis
16.
Braz. j. med. biol. res ; 53(12): e9949, 2020. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132509

ABSTRACT

Acne is a kind of common, chronic skin condition caused by the inflammation of the sebaceous glands in hair follicles. Recent studies have demonstrated that baicalin (BA) possesses potential anti-inflammatory properties. In this study, we evaluated the anti-inflammatory activity of BA in vitro and in vivo. Heat-killed Propionibacterium acnes-induced THP-1 cells and live P. acnes-injected male Sprague Dawley rats were used for establishing the acne model. The rate of ear swelling was calculated, and the severity was determined by hematoxylin and eosin staining. The production of cytokines [interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF-α)] in the cell supernatant and ear tissue homogenates was measured by ELISA. Protein levels of JNK, ERK, P38, IκBα, P65, Nod-like receptor pyrin domain-containing 3 (NLRP3), pro-caspase-1, and IL-1β in THP-1 cells and ear tissues were detected by western blotting. NLRP3 and IL-1β were detected by immunohistochemistry, and the NLRP3, IL-1β and pro-caspase-1 mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that BA decreased the expression of pro-inflammatory cytokines in vitro and in vivo. Moreover, BA down-regulated the phosphorylation of JNK, ERK1/2, and κBα and inhibited the nuclear translocation of p65. Furthermore, BA inhibited the activation of NLRP3 inflammasome, at both the gene and protein levels. Taken together, the results demonstrated that BA might exert its anti-inflammatory activity by inhibiting NF-κB/MAPK signaling pathways and consequently suppressing the activation of the NLRP3 inflammasome both in vivo and in vitro.


Subject(s)
Animals , Male , Rats , Dermatitis/drug therapy , Inflammasomes , Propionibacterium acnes/metabolism , Flavonoids , Signal Transduction , NF-kappa B/metabolism , Rats, Sprague-Dawley , MAP Kinase Signaling System , Interleukin-1beta/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Inflammation/chemically induced , Inflammation/drug therapy
17.
Chinese Medical Journal ; (24): 20-27, 2020.
Article in English | WPRIM | ID: wpr-878002

ABSTRACT

The NOD-like receptor protein 3 (NLRP3) inflammasome is a key regulator of the host's immune response, and many immune and metabolic disorders are linked to its activation. This review aimed to investigate and clarify the relationship between this inflammasome and high-risk reproductive disorders. Papers cited here were retrieved from PubMed up to August 2020 using the keywords "NLRP3" or "NALP3", "caspase-1", "endometriosis", "gestational diabetes", "interleukin (IL)-18", "IL-1β", "pre-eclampsia (PE)", "preterm birth", "polycystic ovarian syndrome (PCOS)", "recurrent spontaneous abortion (RSA)", and combinations of these terms. The results show that NLRP3 inflammasome is associated with various high-risk reproductive disorders and many inflammatory factors are secreted during its activation, such as IL-1β induced during the development of endometriosis. PCOS is also associated with activation of the NLRP3 inflammasome, especially in overweight patients. It also participates in the pathogenesis of RSA and is activated in fetal membranes before preterm birth. The placentas of pregnant women with PE show higher expression of the NLRP3 inflammasome, and gestational diabetes mellitus occurs simultaneously with its activation. Current evidence suggest that the NLRP3 inflammasome plays an important role in female reproductive disorders. New treatment and management methods targeting it might help reduce the incidence of such disorders and improve neonatal outcomes.


Subject(s)
Caspase 1 , Female , Humans , Infant, Newborn , Inflammasomes , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein , NLR Proteins , Pregnancy , Premature Birth , Risk Assessment
18.
Chinese Acupuncture & Moxibustion ; (12): 1323-1327, 2020.
Article in Chinese | WPRIM | ID: wpr-877535

ABSTRACT

OBJECTIVE@#To observe the effect of pretreatment of acupuncture on the expression of nucleotide-binding oligomerization domain-like receptor 3(NLRP3), Caspase-1, interleukin1β(IL-1β) and the number of activated microglia (MG) in the hippocampus in Alzheimer's disease (AD) like rats, so as to explore the mechanism of pretreatment of acupuncture in preventing and treating AD.@*METHODS@#A total of 36 SD rats were randomly divided into a blank group, a model group and an electroacupuncture (EA) group, 12 rats in each group. The AD like rat model was established by 8-week continuous intraperitoneal injection of D-galactose (120 mg·kg@*RESULTS@#Compared with the blank group, the average escape latency was prolonged (@*CONCLUSION@#Pretreatment of acupuncture could prevent and treat the learning-memory dysfunction in AD like rats, and its mechanism may be related to the inhibition of NLRP3 inflammatsome related protein and MG activation.


Subject(s)
Alzheimer Disease/therapy , Animals , Electroacupuncture , Hippocampus , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Rats , Rats, Sprague-Dawley
19.
Article in Chinese | WPRIM | ID: wpr-828655

ABSTRACT

OBJECTIVE@#To study the role of nucleotide-binding oligomerization domain-like receptor proteins 1 and 3 (NLRP1 and NLRP3) inflammasome signaling pathways in the immune mechanism of inflammatory bowel disease (IBD) in children.@*METHODS@#A total of 126 children with IBD were enrolled as the study group, including 32 children with Crohn's disease (CD) and 94 children with ulcerative colitis (UC). A total of 120 children who underwent colectomy were enrolled as the control group. The mRNA expression of NLRP1, NLRP3, Caspase-1, and interleukin-1β (IL-1β) was compared between groups.@*RESULTS@#The study group had significantly higher mRNA expression of NLRP1, NLRP3, Caspase-1, and IL-1β than the control group, and their mRNA expression levels tended to increase with the severity of CD or UC (P<0.05). In the children with UC or CD, the mRNA expression levels of NLRP1, NLRP3, Caspase-1, and IL-1β were positively correlated with serum IgM and IgG levels (P<0.05), and the mRNA expression levels of NLRP1 and NLRP3 were positively correlated with those of Caspase-1 and IL-1β (P<0.05).@*CONCLUSIONS@#The NLRP1 and NLRP3 inflammasome signaling pathways may regulate the immune mechanism of IBD in children by upregulating the expression of Caspase-1 and IL-1β.


Subject(s)
Adaptor Proteins, Signal Transducing , Apoptosis Regulatory Proteins , Child , Humans , Inflammasomes , Inflammatory Bowel Diseases , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein , Signal Transduction
20.
Acta Physiologica Sinica ; (6): 455-462, 2020.
Article in Chinese | WPRIM | ID: wpr-827041

ABSTRACT

The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1β, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1β, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.


Subject(s)
Animals , Caspase 1 , Gene Expression , Hippocampus , Inflammasomes , Insulin Resistance , Male , Mice , Mice, Inbred C57BL , NIMA-Related Kinases , NLR Family, Pyrin Domain-Containing 3 Protein , Physical Conditioning, Animal , Pyroptosis
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