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Objective:To explore the protective effect of 18α glycyrrhetinic acid (18α-GA) on acute ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice, providing theoretical and experimental basis for the clinical application of 18α-GA.Methods:Forty male C57BL/6J mice were randomly divided into 5 groups: DSS model group, positive drug control group, high, medium, and low dose groups of 18α-GA, with 8 mice in each group. The 5 groups of mice were continuously fed with 3% DSS solution for 7 days to establish an acute UC animal model. At the same time, each group was intraperitoneally injected with 100 mg/kg physiological saline, 100 mg/kg sulfasalazine, 40 mg/kg 18α-GA, 20 mg/kg 18α-GA, and 10 mg/kg 18α-GA daily. The weight of mice was measured and recorded daily, and the Disease Activity Index (DAI) of mice was evaluated. On the 8th day, the mice were euthanized and their colon length was measured; After slicing, the colon mucosa was observed and pathological scoring was performed; Western blot was used to detect the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway related proteins in colon tissue; Enzyme linked immunosorbent assay (ELISA) was used to determine the content of interleukin(IL)-1β in colon tissue.Results:Compared with the DSS model group, the weight loss amplitude of the 18α-GA high and medium dose groups was significantly smaller on the 7th day (all P<0.05); Colon length was longer (all P<0.05), the pathological score of colon mucosa was significantly lower (all P<0.05); The expression of GSDMD, cleaved caspase1, and IL-1β in colon tissue was significantly lower (all P<0.05); The 18α-GA high-dose group had lower DAI scores ( P<0.05); The expression of NLRP3 was lower in colon tissue ( P<0.05). Conclusions:18α-GA can improve DSS induced acute ulcerative colitis in mice by inhibiting the activation of NLRP3 inflammasome pathway.
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Context: Periodontitis is an inflammatory disease which is ubiquitous. When there is an onset of infection, the innate immunity gets activated followed by the adaptive immune system. Inflammasomes identify the pathogen-associated molecular patterns or danger-associated molecular patterns and initiate inflammation. Nod- like receptor family pyrin domain-containing protein 3 (NLRP 3) is a protein belonging to the intracellular innate immune sensors that act against bacteria. The inflammasome acts along with the toll-like receptor pathways to initiate an action against pathogens. NLRP3 (also known as PYPAF-1 or cryopyrin) acts via apoptosis-associated speck-like protein (ASC). Aims: The study aimed at finding out the relation between levels of NLRP3 in chronic periodontitis and healthy subjects via the enzyme-linked immunosorbent assay (ELISA). Settings and Design: This was a Cross-sectional study. Materials and Methods: Clinical examination and saliva sampling of the study population was done. Reagents were prepared and NLRP3 levels were estimated using ELISA analysis. Statistical Analysis: Intergroup comparison was initiated using the unpaired t-test and for within the group (intragroup), the two-way analysis of variance was used. The Pearson correlation coefficient helped to determine the strength of linear association. Results: Increased levels of NLRP3 were seen in subjects suffering from chronic periodontitis. NLRP3 was also seen to be positively correlated to probing pocket depth, clinical attachment loss, gingival index, and plaque index. Conclusions: A positive correlation exists between NLRP3 and chronic periodontitis, and hence, NLRP3 can be a potential biomarker.
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OBJECTIVE: The aim: This study aimed to evaluate the NLRP3 immunoreactivity in ulcerative colitis in various clinical presentations. PATIENTS AND METHODS: Materials and methods: The retrospective study involved 80 formalin fixed paraffin embedded tissue blocks. These were divided into 50 samples of ulcerative colitis and 30 with normal colonoscopy findings. NLRP3 protein expression patterns were evaluated in various cellular components in tissue sections using immunohistochemistry method. RESULTS: Results: NLRP3 inflammasome was significantly expressed with higher percentage among ulcerative colitis tissue sections compared with normal tissue sections. Intense staining was observed in Paneth cells at the base of crypts, inflammatory cells infiltrated between glands and near the base of crypts. Variable intensities of NLRP3 staining were observed in surface epithelial cells and glandular epithelium. Statically higher percentage of expression was found among active disease and patients with extra-intestinal complications. CONCLUSION: Conclusions: The NLRP3 protein expression pattern was upregulated among various cellular compartments among ulcerative colitis and correlated with disease activity.
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Colitis Ulcerosa , Proteína con Dominio Pirina 3 de la Familia NLR , Células Epiteliales , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estudios RetrospectivosRESUMEN
The progression of periodontitis depends on interactions between the periodontal pathogens and the host immune cytokines, including interleukin (IL)-1ß and IL-18. Production of IL-1ß is regulated by NOD-like receptors family pyrin domain containing 3 (NLRP3). This study aimed to evaluate the effect of periodontal treatment on the concentrations of IL-18 and NLRP3 in patients with chronic periodontitis. In this experimental study, 18 patients with chronic periodontitis and a mean age of 46.2±8.95 years, were included. The gingival crevicular fluid (GCF) was collected at the beginning of the study, 4 weeks after non-surgical (phase I), and 4 weeks after surgical periodontal treatment. The levels of NLRP3 and IL-18 were measured; using an enzyme-linked immunosorbent assay. Pearson correlation test was used to analyze the concentration of NLRP3 and IL-18 before and after the treatments with CAL and PD. There was a significant association between the level of NLRP3 and the mean values of PD and CAL before treatment. After each treatment phase, a significant decrease was observed in the NLRP3 level. There was no significant relationship between IL-18 and clinical parameters before and after periodontal treatments. Given the possible association between the level of NLRP3 and clinical parameters, we suggest it as a possible indicator of inflammation in chronic periodontitis and an index for evaluating the treatment outcome.
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Periodontitis Crónica/inmunología , Periodontitis Crónica/terapia , Interleucina-18/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Adulto , Biomarcadores/metabolismo , Periodontitis Crónica/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-18/inmunología , Masculino , Persona de Mediana Edad , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: Obesity is a correctable factor for uncontrolled bronchial asthma. However, the effects of glucagon-like peptide-1 receptor (GLP-1R) agonist, a recently approved antiobestic drug, on airway hyperresponsiveness (AHR) and immune responses are not known. METHODS: Mice were fed with high-fat diet (HFD, 60% fat) for 8 weeks to induce obesity. Ovalbumin (OVA) sensitization and challenges were performed for 7 weeks. The mice were injected intraperitoneally with GLP-1R agonist 5 times a week for 4 weeks after OVA sensitization. After AHR measurement, expression of Th2, Th17 cytokines, and interleukin (IL)-33 were measured in BALF and lung tissues. Moreover, IL-1ß and activity level of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were analyzed to investigate the mechanism of GLP-1R agonist on asthmatic airway inflammation. RESULTS: HFD induced significant weight gain, OVA sensitization and challenge in obese mice made eosinophilic airway inflammation, and increased AHR. Treatment with GLP-1R agonist-induced weight loss suppressed eosinophilic airway inflammation and decreased AHR. Expression of IL-4, 5, and 33 was increased in BALF of obese asthma mice followed by a decrease in response to GLP-1R agonist treatment. Moreover, lung tissue H&E stain revealed that peribronchial inflammation induced by obesity and OVA was effectively suppressed by GLP-1R agonist. Expressions of NLRP3, activated caspase-1, and IL-1ß were increased in lung tissues of obese asthma mice and demonstrated a decrease in response to GLP-1R agonist treatment. CONCLUSIONS: GLP-1R agonist effectively induced weight loss, suppressed eosinophilic bronchial airway inflammation, and AHR in obese asthma mice. These effects were mediated by suppression of NLRP3 inflammasome activity and IL-1ß. GLP-1R agonist is proposed as a novel anti-asthmatic agent targeting the obese asthmatics.
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Asma , Preparaciones Farmacéuticas , Animales , Asma/tratamiento farmacológico , Modelos Animales de Enfermedad , Péptido 1 Similar al Glucagón , Inflamasomas , Inflamación , Ratones , Ratones Endogámicos BALB C , Ratones Obesos , Proteína con Dominio Pirina 3 de la Familia NLR , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , OvalbúminaRESUMEN
BACKGROUND: Inflammation promotes immune cell infiltration into tissues and induces production of pro-inflammatory cytokines that mediate innate immune responses. Acute or temporary inflammation results in the required repair of the inflamed tissues. However, chronic inflammation leads to pathogenesis of inflammatory conditions such as periodontal disease. In periodontal tissues, pro-inflammatory cytokines mediate inflammatory responses and accelerate the bone-resorbing activity of osteoclasts, resulting in destruction of alveolar bone. Levels of interleukin-1 (IL-1), a major pro-inflammatory cytokine that strongly promotes osteoclastic activity, are elevated in oral tissues of patients with periodontitis. Therefore, elucidation of the mechanisms underlying IL-1 production will enhance our understanding of the pathogenesis of periodontal disease. HIGHLIGHT: IL-1 has two isoforms: IL-1α and IL-1ß. Both isoforms bind to the same IL-1 receptor and have identical biological activity. Unlike that of IL-1α, the IL-1ß precursor is not bioactive. To induce its bioactivity, the IL-1ß precursor is cleaved by caspase-1, whose activation is mediated by multiprotein complexes termed inflammasomes. Thus, IL-1ß maturation and activity are strictly regulated by inflammasomes. This review highlights the current understanding of the molecular mechanisms underlying IL-1 production and the related inflammasome activity. CONCLUSION: Inhibition of IL-1 production or the inflammasomes via their regulatory mechanisms may facilitate prevention or treatment of periodontal disease and other inflammatory diseases.
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Inflamasomas , Enfermedades Periodontales , Caspasa 1 , Humanos , Inflamación , Interleucina-1/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLRRESUMEN
Objective: To investigate the effect of electroacupuncture (EA) on cognitive function in D-galactose (D-gal)-induced aging rats, and the correlation between the effect and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3)-ASC-Caspase-1 signaling pathway. Methods: Forty-six male Sprague-Dawley (SD) rats were randomly divided into a control group (n=10), a model group (n=12), an EA-7 d group (n=12) and an EA-21 d group (n=12). Except the control group, the other three groups received 42 consecutive days of intraperitoneal injection of D-gal to establish aging rat models with cognitive dysfunction. The control group received the same amount of normal saline via intraperitoneal injection. Two EA groups were given EA therapy for 21 consecutive days (began from the 22nd day of modeling) or 7 consecutive days (began from the 36th day of modeling) accordingly at Dazhui (GV 14), Baihui (GV 20), Shenshu (BL 23) and Zusanli (ST 36). After modeling/ intervention, all four groups received behavioral evaluations by Morris water maze (MWM) test, novel object recognition (NOR) test and step-down passive avoidance (SDPA) test followed by the Western blot (WB) detection of the expression levels of hippocampal NLRP3 inflammasome-associated proteins NLRP3, ASC and Caspase-1. Results: MWM (place navigation test, PNT) results showed that the escape latency in the model group was significantly longer than that in the other three groups (P<0.05), and there was no significant difference among the other three groups on the 1st day of the test (P>0.05). From the 2nd day to the 4th day of the test, there was no significant difference between the EA-21 d group and the control group (P>0.05) in the escape latency; the escape latency was significantly shorter in the EA-21 d group than in the model group and the EA-7 d group (P<0.05). MWM (spatial probe test, SPT) results showed that the time spent in the target quadrant was significantly shorter and platform crossover number was significantly lower in the model group than in the other three groups (P<0.05). The time spent in the target quadrant was longer in the EA-7 d group than in the model group (P<0.05), but was shorter than that in the control group and the EA-21 d group (P<0.05). There was no significant difference in the swimming speed among the four groups (P>0.05). NOR results showed that there was no significant difference in the recognition ratio between the EA-7 d group and the EA-21 d group (P>0.05), and the recognition ratio was significantly higher in the two EA groups than in the model group (P<0.05), but was lower than in the control group (P<0.05). SDPA results showed that the electric shock number was higher in the model group than in the other three groups (P<0.05), and the differences among the other three groups were statistically insignificant (P>0.05). The model group had the shortest step-down latency, followed by the EA-7 d group, the EA-21 d group and the control group in order (P<0.05). The WB results indicated that the expression level of NLRP3 was significantly lower in the control group and the EA-21 d group than in the model group and the EA-7 d group (P<0.05). The expression levels of ASC and Caspase-1 were significantly higher in the model group than in the other three groups (P<0.05), and there was no significant difference among these three groups (P>0.05). Conclusion: NLRP3 inflammasome may be involved in the development of cognitive decline in aging rats; 7 consecutive days of EA intervention can partially improve the cognitive impairment in aging rats though the effect is rather limited; 21 consecutive days of EA intervention may improve the learning and memory abilities in aging rats via downregulating the expression levels of NLRP3 inflammasome-associated proteins in hippocampus.
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Objectives: The present study was conducted to investigate the protective effects of chamomile oil from Matricaria chamomilla against type 1 diabetes mellitus (T1DM) and its potential mechanisms. Methods: T1DM was established in male New Zealand white rabbits via a single intraperitoneal infusion of streptozotocin (STZ) (80 mg/kg body weight−1, dissolved in 0.2 mL of normal saline). Different doses of chamomile oil (25, 50 and 100 mg/kg) were orally administrated to STZ induced diabetic rabbits for 21 consecutive days. The expression of pro-inflammatory cytokines was determined using ELISA assay. The expression of NF-κB and NLRP3 was measured using Western blot assay. Results: Compared with normal rabbits, STZ-induced diabetic rabbits exhibited significant increased levels of blood glucose and decreased levels of serum insulin that were reversed using middle and high tested dose of chamomile oil. Likewise, STZ-induced diabetic rabbits showed a significant increased expression of NF-κB and NLRP3 proteins in the pancreas tissue that was reversed by high tested dose of chamomile oil. Conclusion: Collectively, our findings demonstrated that chamomile oil possesses anti-hyperglycemic, and anti-inflammatory activities in STZ-induced diabetic rabbits by targeting inflammatory cytokines and NF-κB and NLRP3 signaling pathways.
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Objective: To observe the effects of moxibustion on colonic inflammation, and the expressions of ubiquitin and nucleotide-binding oligomerization domain (Nod)-like receptor protein 3 (NLRP3) proteins in rats with ulcerative colitis (UC), and to explore the anti-inflammatory mechanism of moxibustion in the UC treatment. Methods: Clean grade male Sprague-Dawley (SD) rats were randomly divided into a normal group (NG), a model group (MG), a moxa-stick moxibustion group (MSMG) and a Western medicine group (WMG). UC model was prepared by freely drinking 35 g/L dextran sulfate sodium (DSS) solution. Bilateral Tianshu (ST 25) were selected for mild moxibustion treatment in the MSMG; mesalazine solution was intragastrically administrated in the WMG. Rats in the NG and MG were only grasped and fixed as in the MSMG without any treatment. After treatment, hematoxylin-eosin (HE) staining was performed to observe and score the colonic pathological damage under light microscope; immunofluorescence method was used to determine the expression of colonic ubiquitin protein; immunohistochemical method was used to detect the expressions of colonic interleukin (IL)-1β and NLRP3 proteins. Results: The colon tissue was severely injured, and the pathological score was significantly increased in the MG than in the NG (P<0.01), and the protein expressions of ubiquitin, NLRP3 and IL-1β in the colon were significantly increased (all P<0.01). Compared with the MG, the colonic damage was repaired, the inflammation and pathological scores were reduced, and the ubiquitin, NLRP3 and IL-1β protein expressions were decreased in the MSMG and WMG (all P<0.01). Correlation analysis revealed that the ubiquitin protein expression was correlated with the colonic pathological score and the NLRP3 protein expression (r=0.677, P<0.01; r=0.536, P<0.05). Conclusion: Moxibustion can down-regulate the protein expressions of ubiquitin, NLRP3 and IL-1β in the colon of UC rats, which may be one of the mechanisms to promote the repair of colonic inflammatory lesions and exert anti-inflammatory effects.
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Objectives: The present study was conducted to investigate the protective effects of chamomile oil from Matricaria chamomilla against type 1 diabetes mellitus (T1DM) and its potential mechanisms. Methods: T1DM was established in male New Zealand white rabbits via a single intraperitoneal infusion of streptozotocin (STZ) (80 mg/kg body weight-1, dissolved in 0.2 mL of normal saline). Different doses of chamomile oil (25, 50 and 100 mg/kg) were orally administrated to STZ induced diabetic rabbits for 21 consecutive days. The expression of pro-inflammatory cytokines was determined using ELISA assay. The expression of NF-κB and NLRP3 was measured using Western blot assay. Results: Compared with normal rabbits, STZ-induced diabetic rabbits exhibited significant increased levels of blood glucose and decreased levels of serum insulin that were reversed using middle and high tested dose of chamomile oil. Likewise, STZ-induced diabetic rabbits showed a significant increased expression of NF-κB and NLRP3 proteins in the pancreas tissue that was reversed by high tested dose of chamomile oil. Conclusion: Collectively, our findings demonstrated that chamomile oil possesses anti-hyperglycemic, and anti-inflammatory activities in STZ-induced diabetic rabbits by targeting inflammatory cytokines and NF-κB and NLRP3 signaling pathways.
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Cryopyrin-associated periodic syndrome (CAPS) is a hereditary autoinflammatory syndrome caused by mutations in NLRP3 (encoding cryopyrin), which presents with fever, fatigue and arthralgia. Thus far, however there have been no reports of CAPS in Korea. Herein, we report 3 cases of CAPS for the first time in Korea. The first case, a 28-year-old man with recurrent urticaria, arthralgia and fever induced by cold, all of which were observed in his father, showed elevated erythrocyte sedimentation rate and C-reactive protein. He exhibited a p.Gly303Asp variant of the NLPR3 gene. The second case, a 2-year-old girl who had recurrent urticaria, arthritis and oral and genital ulcers, was positive for HLA B51 and a p.Glu569Lys mutation in exon 3 of the NLRP3 gene. Administration of anakinra greatly improved her symptoms. The third case, a 4-year-old boy who presented with recurrent urticaria, arthralgia, and fever, exhibited a p.Val72Met mutation in exon 1 of the NLRP3 gene. Administration of tocilizumab improved all of his symptoms. This small case series suggests that clinicians consider CAPS and conduct genetic studies when arthralgia and fever are accompanied by urticaria in Korea.
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Cryopyrin-associated periodic syndrome (CAPS) is a hereditary autoinflammatory syndrome caused by mutations in NLRP3 (encoding cryopyrin), which presents with fever, fatigue and arthralgia. Thus far, however there have been no reports of CAPS in Korea. Herein, we report 3 cases of CAPS for the first time in Korea. The first case, a 28-year-old man with recurrent urticaria, arthralgia and fever induced by cold, all of which were observed in his father, showed elevated erythrocyte sedimentation rate and C-reactive protein. He exhibited a p.Gly303Asp variant of the NLPR3 gene. The second case, a 2-year-old girl who had recurrent urticaria, arthritis and oral and genital ulcers, was positive for HLA B51 and a p.Glu569Lys mutation in exon 3 of the NLRP3 gene. Administration of anakinra greatly improved her symptoms. The third case, a 4-year-old boy who presented with recurrent urticaria, arthralgia, and fever, exhibited a p.Val72Met mutation in exon 1 of the NLRP3 gene. Administration of tocilizumab improved all of his symptoms. This small case series suggests that clinicians consider CAPS and conduct genetic studies when arthralgia and fever are accompanied by urticaria in Korea.
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Adulto , Preescolar , Femenino , Humanos , Masculino , Artralgia , Artritis , Sedimentación Sanguínea , Proteína C-Reactiva , Síndromes Periódicos Asociados a Criopirina , Exones , Padre , Fatiga , Fiebre , Proteína Antagonista del Receptor de Interleucina 1 , Corea (Geográfico) , Úlcera , UrticariaRESUMEN
BACKGROUND: Obesity is associated with infiltration of macrophages into adipose tissue. However, effects of obesity on macrophage infiltration and activation in periodontal tissues with periodontitis are still to be elucidated. METHODS: A diet-induced obesity 16-week mouse model was constructed, and periodontitis was induced by periodontal ligation for 10 days. The model consisted of periodontitis (P) and control (C) groups, with high fat (HF) and normal (N) diet conditions. Bone loss (BL) was analyzed by microcomputed tomography. In periodontal tissues, immunohistochemical staining and quantitative polymerase chain reaction (qPCR) detected expressions of: 1) nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway; 2) macrophage-specific marker (F4/80); and 3) macrophage chemotactic protein 1 (MCP1). Bone marrow-derived macrophages (BMDMs) from the mouse model were stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS) in vitro (NC/NC + LPS: BMDMs from NC group without/with LPS stimulation; HFC/HFC + LPS: BMDMs from HFC group without/with LPS stimulation). Expressions of NLRP3 pathway in BMDMs were detected by immunocytochemical staining and qPCR. RESULTS: BL increased significantly with periodontitis (NC versus NP; HFC versus HFP) and obesity (NP versus HFP). Expressions of NLRP3 pathway were significantly elevated in gingival tissues with periodontitis (NC versus NP; HFC versus HFP), but not with obesity (NC versus HFC; NP versus HFP). F4/80 and MCP1 expressions were significantly upregulated in gingival tissues with periodontitis (NC versus NP; HFC versus HFP) but significantly downregulated in the context of obesity (NP versus HFP). In vitro, NLRP3 pathway expressions were significantly upregulated in BMDMs after LPS stimulation (NC + LPS versus NC; HFC + LPS versus HFC), but significantly downregulated in HFC groups (HFC versus NC; HFC + LPS versus NC + LPS). CONCLUSION: Obesity may paralyze innate immune response of periodontium via attenuating infiltration and activation of macrophages and further aggravate periodontal disease.
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Macrófagos , Proteína Adaptadora de Señalización NOD2/metabolismo , Nucleótidos/metabolismo , Obesidad/fisiopatología , Animales , Lipopolisacáridos , Ratones , Modelos Animales , Porphyromonas gingivalis , Microtomografía por Rayos XRESUMEN
BACKGROUND: The NLRP3 inflammasome is essentially a family of intracellular innate immune sensors that can respond to bacterial challenge and initiate early host immunity responses. However, the involvement and possible molecular mechanism of the NLRP3 pathway in the context of chronic periodontitis (CP) and diabetes mellitus have yet to be fully elucidated. METHODS: Gingival tissues were collected from patients with CP and/or type 2 diabetes mellitus (T2DM), and the expression of NLRP3 and interleukin (IL)-1ß was analyzed by immunohistochemistry. To explore the possible molecular mechanism, human gingival epithelial cells (HGECs) were established in vitro and challenged with lipopolysaccharide (LPS) and/or high glucose. High extracellular K(+) was applied as an inhibitor of NLRP3. The NLRP3 pathway was analyzed by immunocytochemistry and quantitative polymerase chain reaction. RESULTS: Compared with control individuals, NLRP3 and IL-1ß were significantly upregulated in oral gingival epithelium of patients with CP and/or T2DM (P <0.05). The expression of NLRP3 was significantly upregulated in HGECs when stimulated in vitro by LPS or high glucose (P = 0.00). The simultaneous stimulation of LPS and high glucose contributed to significant upregulation of NLRP3 expression versus LPS or high glucose alone (P = 0.00). Although expression of caspase 1 and IL-1ß protein were increased in HGECs when stimulated by LPS, they were partially inhibited after the NLRP3 was successfully blocked. CONCLUSION: For patients with T2DM and CP, hyperglycemic status may exacerbate the inflammation state of gingival tissue by activating the NLRP3 pathway, and this abnormal host inflammatory response may contribute to further tissue breakdown.
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Proteínas Portadoras/inmunología , Periodontitis Crónica/inmunología , Encía/inmunología , Hiperglucemia/complicaciones , Inmunidad Innata/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Portadoras/análisis , Proteínas Portadoras/antagonistas & inhibidores , Caspasa 1/análisis , Caspasa 1/inmunología , Células Cultivadas , Diabetes Mellitus Tipo 2/inmunología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Femenino , Encía/citología , Glucosa/inmunología , Humanos , Interleucina-1beta/análisis , Interleucina-1beta/inmunología , Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , Proteína con Dominio Pirina 3 de la Familia NLR , Potasio/farmacología , Transducción de Señal/inmunología , Adulto JovenRESUMEN
Inflammasomes are cytosolic multiprotein complexes that sense microbial motifs or cellular stress and stimulate caspase-1-dependent cytokine secretion and cell death. Recently, it has become increasingly evident that both DNA and RNA viruses activate inflammasomes, which control innate and adaptive immune responses against viral infections. In addition, recent studies suggest that certain microbiota induce inflammasomes-dependent adaptive immunity against influenza virus infections. Here, we review recent advances in research into the role of inflammasomes in antiviral immunity.
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Inflammasomes are cytosolic multiprotein complexes that sense microbial motifs or cellular stress and stimulate caspase-1-dependent cytokine secretion and cell death. Recently, it has become increasingly evident that both DNA and RNA viruses activate inflammasomes, which control innate and adaptive immune responses against viral infections. In addition, recent studies suggest that certain microbiota induce inflammasomes-dependent adaptive immunity against influenza virus infections. Here, we review recent advances in research into the role of inflammasomes in antiviral immunity.
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Inmunidad Adaptativa , Muerte Celular , Citosol , Células Dendríticas , ADN , Inflamasomas , Vacunas contra la Influenza , Gripe Humana , Metagenoma , Microbiota , Complejos Multiproteicos , Orthomyxoviridae , Virus ARNRESUMEN
The inflammasome is a multi-protein complex that induces maturation of inflammatory cytokines interleukin (IL)-1ß and IL-18 through activation of caspase-1. Several nucleotide binding oligomerization domain-like receptor family members, including NLRP3, recognize unique microbial and danger components and play a central role in inflammasome activation. The NLRP3 inflammasome is critical for maintenance of homeostasis against pathogenic infections. However, inflammasome activation acts as a double-edged sword for various bacterial infections. When the IL-1 family of cytokines is secreted excessively, they cause tissue damage and extensive inflammatory responses that are potentially hazardous for the host. Emerging evidence has shown that diverse bacterial pathogens or their components negatively regulate inflammasome activation to escape the immune response. In this review, we discuss the current knowledge of the roles and regulation of the NLRP3 inflammasome during bacterial infections. Activation and regulation of the NLRP3 inflammasome should be tightly controlled to prevent virulence and pathology during infections. Understanding the roles and regulatory mechanisms of the NLRP3 inflammasome is essential for developing potential treatment approaches against pathogenic infections.
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Proteínas Portadoras/metabolismo , Inflamasomas/metabolismo , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/patología , Infecciones Bacterianas/prevención & control , Caspasa 1/metabolismo , Humanos , Inflamasomas/inmunología , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de SeñalRESUMEN
BACKGROUND: The molecular basis for the focal nature of atherosclerotic lesions is poorly understood. Here, we explored whether disturbed flow patterns activate an innate immune response to form the NLRP3 inflammasome scaffold in vascular endothelial cells via sterol regulatory element binding protein 2 (SREBP2). METHODS AND RESULTS: Oscillatory flow activates SREBP2 and induces NLRP3 inflammasome in endothelial cells. The underlying mechanisms involve SREBP2 transactivating NADPH oxidase 2 and NLRP3. Consistently, SREBP2, NADPH oxidase 2, and NLRP3 levels were elevated in atheroprone areas of mouse aortas, suggesting that the SREBP2-activated NLRP3 inflammasome causes functionally disturbed endothelium with increased inflammation. Mimicking the effect of atheroprone flow, endothelial cell-specific overexpression of the activated form of SREBP2 synergized with hyperlipidemia to increase atherosclerosis in the atheroresistant areas of mouse aortas. CONCLUSIONS: Atheroprone flow induces NLRP3 inflammasome in endothelium through SREBP2 activation. This increased innate immunity in endothelium synergizes with hyperlipidemia to cause topographical distribution of atherosclerotic lesions.
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Aterosclerosis/inmunología , Proteínas Portadoras/inmunología , Proteína 2 de Unión a Elementos Reguladores de Esteroles/inmunología , Vasculitis/inmunología , Animales , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Hemodinámica/inmunología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunidad Innata/inmunología , Inflamasomas/inmunología , Inflamasomas/metabolismo , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Transgénicos , MicroARNs/inmunología , MicroARNs/metabolismo , NADPH Oxidasa 2 , NADPH Oxidasas/inmunología , NADPH Oxidasas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , ARN Interferente Pequeño/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Estrés Mecánico , Vasculitis/genética , Vasculitis/metabolismoRESUMEN
The inflammasome is a multi-protein complex that induces maturation of inflammatory cytokines interleukin (IL)-1beta and IL-18 through activation of caspase-1. Several nucleotide binding oligomerization domain-like receptor family members, including NLRP3, recognize unique microbial and danger components and play a central role in inflammasome activation. The NLRP3 inflammasome is critical for maintenance of homeostasis against pathogenic infections. However, inflammasome activation acts as a double-edged sword for various bacterial infections. When the IL-1 family of cytokines is secreted excessively, they cause tissue damage and extensive inflammatory responses that are potentially hazardous for the host. Emerging evidence has shown that diverse bacterial pathogens or their components negatively regulate inflammasome activation to escape the immune response. In this review, we discuss the current knowledge of the roles and regulation of the NLRP3 inflammasome during bacterial infections. Activation and regulation of the NLRP3 inflammasome should be tightly controlled to prevent virulence and pathology during infections. Understanding the roles and regulatory mechanisms of the NLRP3 inflammasome is essential for developing potential treatment approaches against pathogenic infections.
Asunto(s)
Humanos , Infecciones Bacterianas/inmunología , Proteínas Portadoras/metabolismo , Caspasa 1/metabolismo , Inflamasomas/inmunología , Interleucina-1beta/metabolismo , Transducción de SeñalRESUMEN
Context: Autoinflammatory syndromes are diseases manifested by recurrent episodes of fever and inflammation in multiple organs. There is no production of autoantibodies, but interleukins play an important role and acute-phase reactants show abnormalities. Our aim was to report on three cases of autoinflammatory syndromes that are considered to be rare entities. CASE REPORTS: The authors describe the clinical features of three patients whose diagnosis were the following: tumor necrosis factor receptor-associated periodic syndrome (TRAPS), chronic infantile neurological cutaneous articular (CINCA) syndrome and familial Mediterranean fever (FMF). All of the patients presented fever, joint or bone involvement and increased acute phase reactants. The genetic analysis confirmed the diagnoses of two patients. The great diversity of manifestations and the difficulties in genetic analyses make the diagnosing of these diseases a challenge.
Contexto: As síndromes auto-inflamatórias são doenças que se manifestam por surtos recorrentes de febre e inflamação em diversos órgãos. Não ocorre a formação de auto-anticorpos, as interleucinas representam um papel importante e as provas de fase aguda estão alteradas. O nosso objetivo foi relatar três casos de síndromes auto-inflamatórias consideradas como entidades raras. RELATO DE CASOS: Os autores descrevem as características clínicas de três pacientes que tiveram os seguintes diagnósticos: síndrome periódica associada ao receptor do fator de necrose tumoral α (TRAPS), síndrome articular cutânea neurológica e infantil crônica (CINCA) e febre familiar do Mediterrâneo (FFM). Todos os pacientes tiveram em comum a febre, o comprometimento articular ou ósseo e o aumento de provas de fase aguda. O estudo genético confirmou o diagnóstico em dois pacientes. A grande variedade de manifestações e a dificuldade nos estudos genéticos tornam o diagnóstico destas doenças um desafio.