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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 English | WPRIM | ID: wpr-880636

ABSTRACT

OBJECTIVES@#Inflammation especially the overexpression of inflammasome and inflammatory cytokines, is one of the important reasons that affect the occurrence and development of acute cerebral infarction, including the initiation of cerebral infarction, the progress and recovery of post-infarction injury. This study aims to explore expressions of absent in melanoma 2 (AIM2), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in plasma of patients with acute cerebral infarction and its significance.@*METHODS@#A total of 85 patients with acute cerebral infarction were enrolled in the cerebral infarction group. They were assigned into mild, moderate, and severe groups according to the severity of neurological deficits. They were assigned into small, middle, and large cerebral infarction groups according to the area of cerebral infarction. They were assigned into a good prognosis group and a poor prognosis group according to the Modified Rankin Scale (mRS) score on the 90th day after the onset. A total of 85 healthy controls were selected as a control group. The levels of AIM2, IL-1β, and IL-18 in plasma of the cerebral group and the control group were detected by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#The levels of plasma AIM2, IL-1β, and IL-18 in the cerebral infarction group were significantly higher than those in the control group (all @*CONCLUSIONS@#Expressions of AIM2, IL-1β, and IL-18 are up-regulated in the plasma of patients with acute cerebral infarction, and they are closely related to the severity of neurological deficit, cerebral infarction area, and prognosis in patients with acute cerebral infarction, suggesting that AIM2, IL-1β, and IL-18 may play an important role in the occurrence and development of acute cerebral infarction.


Subject(s)
Cerebral Infarction , DNA-Binding Proteins , Humans , Interleukin-18 , Interleukin-1beta , Melanoma , Plasma , Stroke
3.
Article in English | WPRIM | ID: wpr-880618

ABSTRACT

OBJECTIVES@#Chondrocyte apoptosis is an important process in the pathogenesis of osteoarthritis. Mangiferin exerts multiple pharmacological effects such as anti-inflammatory and anti-apoptosis. However, the role of mangiferin in chondrocyte apoptosis is not clear. In this study, we aimed to explore the role of mangiferin in IL-1β-induced chondrocyte apoptosis.@*METHODS@#ATDC5 cells were randomly divided into a control group, a IL-1β group, a MFN-L group, a MFN-M group, a MFN-H group and a MFN+LY294002 group. Cells in the control group were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN-L group, the MFN-M group and the MFN-H group were pretreated with 5, 10 and 20 μmol/L mangiferin for 1 h respectively, and then they were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN+LY294002 group were treated with LY294002 (25 μmol/L) for 1 h, then mangiferin (20 μmol/L) and IL-1β (10 ng/mL) for 1 h and 24 h, respectively. Cell viability was detected by CCK-8 assay and cell apoptosis was measured by flow cytometry. Colorimetric assay was conducted to measure the caspase-3 activity. The protein levels of Bcl-2, Bax, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway related proteins were detected by Western blotting.@*RESULTS@#Compared to the control group, cell viability was significantly decreased; cell apoptosis, caspase-3 activity and Bax protein expression were significantly increased; the protein levels of Bcl-2, p-PI3K, and p-Akt were significantly decreased in the IL-1β group (all @*CONCLUSIONS@#Mangiferin could attenuate IL-1β-induced apoptosis of the mice chondrocytes, which is mediated by the activation of PI3K/Akt signaling pathway.


Subject(s)
Animals , Apoptosis , Chondrocytes , Interleukin-1beta , Mice , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Xanthones
4.
Braz. arch. biol. technol ; 64: e21210256, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339311

ABSTRACT

Abstract While the role of cytokines in celiac disease has been investigated in detail, cytokine release in the event of the exposure of healthy subjects to glutens has only recently been studied. This study was aimed at determining the effects of corn and wheat glutens, incorporated as protein sources into the diet, on serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and the immunohistochemical distribution of CD3 and CD8 receptors in the small intestine in male rats. The study material comprised 24 twenty-day-old male Wistar albino rats, which were randomly assigned in equal numbers to three groups (2 rats/replicate and 4 replicates/group). The feed rations provided to all three groups contained high levels of proteins, which were soybean meal, corn gluten and wheat gluten in the control, corn and wheat groups, respectively. The in Control, Corn and Wheat groups serum IL-1 beta and TNF-alpha levels respectively 55.83 - 46.37; 81.65 - 61.95 and 81.65-61.31 was determined but these differences were statistically insignificant. Furthermore, immunohistochemical examination demonstrated a mathematical increase to have occurred in the distribution of the CD3 and CD8 receptors in the duodenum, jejunum and ileum samples of the corn and wheat groups. In result, based on the findings obtained in this study, we suggest that the long-term feeding of rats on high levels of gluten causes systemic adverse effects.


Subject(s)
Animals , Rats , Cytokines/drug effects , Tumor Necrosis Factor-alpha/drug effects , Interleukin-1beta/drug effects , Glutens/pharmacology , Immunohistochemistry , Rats, Wistar
5.
J. appl. oral sci ; 29: e20210160, 2021. tab, graf
Article in English | LILACS | ID: biblio-1340107

ABSTRACT

Abstract Objective This study aims to evaluate the effect of ellagic acid (EA) by measuring the levels of alveolar bone resorption and inflammatory and oxidative stress markers in the periodontal tissues and serum on the periodontal repair process related to experimental periodontitis in rats. Methodology Forty Wistar rats were divided into four study groups as follows: Group 1=healthy control (n=10); Group 2=EA control (15 mg/kg)(n=10); Group 3=periodontitis (n=10); Group 4=periodontitis+EA (15 mg/kg) (n=10). The periodontitis model was established by ligating bilateral mandibular first molars for 14 days. Then, rats were given normal saline or EA for another 14 days by gavage administration. Serum and gingiva myeloperoxidase (MPO) activity, 8-hydroxydeoxyguanosine(8-OHdG), and glutathione (GSH) levels were analyzed by ELISA. İmmunohistochemical analysis was used to detect Interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) immunoreactivities in the periodontal tissues. Alveolar bone loss (ABL) and attachment loss (AL) was evaluated by histomorphometry analysis. Results ABL and AL were statistically higher in group 3 than in groups 1, 2 and 4 and in group 4 than in groups 1 and 2 (p<0.05). MPO activities in gingival tissue and serum were significantly increased in group 3 compared to groups 1 and 2 (p<0.05). Significantly higher serum GSH levels, lower gingiva, and serum 8-OHdG levels, and MPO activity were observed in group 4 compared to group 3 (p<0.05). Rats with periodontitis (group 3) expressed significantly higher immunoreactivities of IL-6 and TNF-α and lower IL-10 immunoreactivity compared to those other groups (p<0.05). IL-6 and TNF-α immunoreactivities significantly decreased and IL-10 immunoreactivity increased in group 4 after the use of EA compared to group 3 (p<0.001). Conclusions Our findings showed that EA provides significant improvements on gingival oxidative stress and inflammatory markers and alveolar bone resorption in the repair process associated with experimental periodontitis. Therefore, EA may have a therapeutic potential on periodontitis.


Subject(s)
Animals , Rats , Periodontitis/drug therapy , Alveolar Bone Loss , Tumor Necrosis Factor-alpha , Rats, Wistar , Ellagic Acid/pharmacology , Interleukin-1beta
6.
Article in English | WPRIM | ID: wpr-878441

ABSTRACT

OBJECTIVES@#To study the effect and mechanism of low-level laser irradiation (LLLI) on lipopolysaccharide (LPS)-induced inflammatory injury of human periodontal ligament fibroblasts (hPDLFs).@*METHODS@#hPDLFs were inoculated into well plates and randomly divided into the normal group, LPS group, and LPS+LLLI group. The cells in the normal group were cultured in conventional medium. The hPDLFs in the LPS and LPS+LLLI groups were cultured in RPMI1640 medium containing 1 mg·L@*RESULTS@#Compared with the normal group, the LPS group showed increased apoptosis rate of hPDLFs and intracellular free Ca@*CONCLUSIONS@#LLLI has a protective effect on the inflammatory injury of hPDLFs induced by LPS, and the effect is most obvious when the irradiation intensity is 4 J·cm


Subject(s)
Cells, Cultured , Fibroblasts , Humans , Interleukin-1beta , Lasers , Lipopolysaccharides , Periodontal Ligament , Tumor Necrosis Factor-alpha
8.
Chinese Medical Journal ; (24): 963-970, 2021.
Article in English | WPRIM | ID: wpr-878129

ABSTRACT

BACKGROUND@#Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and bone formation. The aim of the present study was to explore the effects of HDAC4 on Interleukin 1 beta (IL-1β)-induced chondrocyte extracellular matrix degradation and whether it is regulated through the WNT family member 3A (WNT3A)/β-catenin signaling pathway.@*METHODS@#Primary chondrocytes (CC) and human chondrosarcoma cells (SW1353 cells) were treated with IL-1β and the level of HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 cells was silenced using small interfering RNA to detect the effect of HDAC4 knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by IL-1β. After transfection with HDAC4 plasmids, the overexpression efficiency was examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the levels of MMP3 and MMP13 were assayed using Western blotting. After incubation with IL-1β, the translocation of β-catenin into the nucleus was observed using immunofluorescence staining in SW1353 cells to investigate the activation of the WNT3A/β-catenin signaling pathway. Finally, treatment with WNT3A and transfection with glycogen synthase kinase 3 beta (GSK3β) plasmids were assessed for their effects on HDAC4 levels using Western blotting.@*RESULTS@#IL-1β downregulated HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown increased the levels of MMP3 and MMP13, which contributed to the degradation of the extracellular matrix. Overexpression of HDAC4 inhibited IL-1β-induced increases in MMP3 and MMP13. IL-1β upregulated the levels of WNT3A, and WNT3A reduced HDAC4 levels in SW1353 cells. GSK-3β rescued IL-1β-induced downregulation of HDAC4 in SW1353 cells.@*CONCLUSION@#HDAC4 exerted an inhibitory effect on IL-1β-induced extracellular matrix degradation and was regulated partially by the WNT3A/β-catenin signaling pathway.


Subject(s)
Cell Line, Tumor , Cells, Cultured , Chondrocytes/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Histone Deacetylases/genetics , Humans , Interleukin-1beta/pharmacology , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3 , Repressor Proteins , Wnt Signaling Pathway , Wnt3A Protein/genetics , beta Catenin/metabolism
9.
Int. j. morphol ; 38(3): 737-746, June 2020. tab, graf
Article in English | LILACS | ID: biblio-1098314

ABSTRACT

This study aimed to evaluate changes in beige adipocytes at different times of melatonin administration, in the morning (ZT01) or in the evening (ZT11), at 30 mg/kg daily by gavage for 7 weeks or continuously with drinking water in the term of high-calorie diet-induced obesity (HCD). Melatonin received at ZT11 or with drinking water resulted in an increased area of the browning zone in the subcutaneous white adipose tissue (sWAT), even in rats with HCD (compared with Control or HCD, respectively). The beige adipocyte and lipid droplet area after melatonin use were reduced compared to those with HCD and Control, in all administration modes (group ZT01 showed smaller changes compared to ZT11 or with drinking water groups). The fibrosis level decreased and significantly differed in HCD ZT01, HCD ZT11, and HCD water compared to that in HCD; moreover, the lowest value determined in HCD water, reached the control parameters. Furthermore, the IL-1b and IL-8 level was decreased in the HCD groups under melatonin treatment at ZT11 or with drinking water compared to that in HCD. The obtained results suggest that melatonin promotes sWAT browning in rats with diet-induced obesity and influences morphological signs of normal rats depending on the time of administration. Different functional activity of beige adipocytes was observed after melatonin was used depending on the time of administration, resulting in heat production and lipolysis (the relative mass of visceral fat was likewise diminished). More rapid browning was observed when melatonin treatment was performed at 1 h before lights-off (ZT11) or continuously via drinking water. Melatonin acted on beige adipocytes of obese rats through changing some parameters such as the area of adipocytes and lipid drops, the number of lipid drops, the relative area browning of sWAT, and the level of tissue fibrosis.


Este estudio tuvo como objetivo evaluar los cambios en los adipocitos beige en diferentes momentos de la administración de melatonina, en la mañana (ZT01) o por la noche (ZT11). Se administraron 30 mg/kg diariamente por sonda durante 7 semanas o continuamente con agua potable durante el periodo de obesidad inducida por una dieta alta en calorías (HCD). La melatonina recibida en ZT11 o con agua potable resultó en un aumento de área dorada en tejido adiposo blanco subcutáneo (sWAT), incluso en ratas con HCD (en comparación con Control o HCD, respectivamente). El área de gotas de lípidos y adipocitos de color beige después del uso de melatonina se redujo en comparación con aquellos con HCD y Control, en todos los modos de administración (el grupo ZT01 mostró cambios más pequeños en comparación con ZT11 o con grupos de agua potable). El nivel de fibrosis disminuyó y difirió significativamente en HCD ZT01, HCD ZT11 y agua HCD, en comparación con el HCD; además, el valor más bajo determinado en agua HCD alcanzó los parámetros de control. Además, el nivel de IL-1b e IL-8 disminuyó en los grupos HCD bajo tratamiento con melatonina en ZT11 o con agua potable en comparación con el de HCD. Los resultados obtenidos sugieren que la melatonina promueve el dorado sWAT en ratas con obesidad inducida por la dieta e influye en los signos morfológicos de las ratas normales dependiendo del momento de la administración. Se observó una actividad funcional diferente de los adipocitos de color beige después de usar melatonina dependiendo del tiempo de administración, dando como resultado la producción de calor y lipólisis (la masa relativa de grasa visceral también disminuyó). Se observó un ennegrecimiento más rápido cuando el tratamiento con melatonina se realizó 1 h antes de apagar las luces (ZT11) o de forma continua en grupos de agua potable. La melatonina actuó en los adipocitos beige de ratas obesas al cambiar algunos parámetros, como el área de adipocitos y gotas de lípidos, el número de gotas de lípidos, el área relativa de ennegrecimiento de sWAT y el nivel de fibrosis tisular.


Subject(s)
Animals , Male , Rats , Adipocytes, Beige/drug effects , Melatonin/administration & dosage , Obesity , Time Factors , Fibrosis , Adipose Tissue/drug effects , Adipose Tissue/pathology , Interleukin-8/drug effects , Diet , Interleukin-1beta/drug effects
10.
Arq. neuropsiquiatr ; 78(5): 255-261, May 2020. tab, graf
Article in English | LILACS | ID: biblio-1131702

ABSTRACT

ABSTRACT Background: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. Objective: The aim of the present study was to investigate depression and its association with interleukins (IL)-1β and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. Methods: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1β and IL-9 were measured in serum samples of all the patients using ELISA kit. Results: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1β were elevated in Group 3, as compared to the other groups. Conclusion: This study showed positive association between depression and IL-1β, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.


RESUMO Introdução: O diabetes e a depressão comórbidas são condições crônicas prevalentes que afetam negativamente a qualidade de vida (QdV). A inflamação tem sido considerada como um mecanismo integral em pacientes com diabetes e depressão. Objetivo: Investigar a depressão e sua associação com interleucinas (IL)-1β e IL-9 em pacientes diabéticos tipo 2 (DM2) e controles. A QdV em diabéticos também foi avaliada. Métodos: Foram incluídos 80 indivíduos, divididos em três grupos: Grupo 1 - controles saudáveis; Grupo 2 - pacientes com DM2 sem depressão; Grupo 3 - pacientes com DM2 com depressão. A depressão e a QdV foram avaliadas usando o Questionário de Saúde do Paciente (Patient Health Questionnaire - PHQ-9) e a auditoria de QdV dependente de diabetes (Audit of Diabetes-Dependent Quality of Life - ADDQoL), respectivamente. IL-1β e IL-9 foram medidas em amostras de soro de todos os pacientes utilizando kit de ELISA. Resultados: O escore do PHQ no grupo 3 foi significativamente maior em comparação ao grupo 1. Os escores de ADDQoL no grupo 3 foram significativamente maiores em comparação ao grupo 2. Os níveis de IL-9 e IL-1β foram elevados no grupo 3, como em comparação com os outros grupos. Conclusão: Este estudo mostrou associação positiva entre depressão e IL-1β, IL-9 em pacientes com DM2. Além disso, os pacientes diabéticos têm pior QdV, o que é ainda piorado pela presença de depressão. Assim, a avaliação rotineira da presença de depressão é sugerida em pacientes com DM2.


Subject(s)
Humans , Interleukin-9 , Diabetes Mellitus, Type 2 , Quality of Life , Depression , Interleukin-1beta/metabolism
11.
Arq. bras. cardiol ; 114(3): 507-514, mar. 2020. tab, graf
Article in Portuguese | LILACS | ID: biblio-1088885

ABSTRACT

Resumo Fundamento Vários marcadores têm sido avaliados quanto a um potencial impacto nas decisões clínicas ou na predição de mortalidade na síndrome coronariana aguda (SCA), incluindo Netrina-1 e IL-1β. Objetivo Examinamos o valor prognóstico de Netrina-1 e IL-1β em pacientes com SCA (2 anos de acompanhamento). Métodos Avaliamos Netrina-1, IL-1β e outros fatores de risco em amostras de soro de 803 pacientes. Curvas de Kaplan-Meier e regressão de Cox foram usadas para análise de óbito por todas as causas, óbito por doenças cardiovasculares (DCV) e desfecho combinado de infarto agudo do miocárdio (IAM) fatal ou novo IAM não fatal, considerando p < 0,05. Resultados Houve 115 óbitos por todas as causas, 78 óbitos por DCV e 67 eventos no desfecho combinado. Níveis de Netrina-1 acima da mediana (> 44,8 pg/mL) foram associados a pior prognóstico (óbito por todas as causas e por DCV) em mulheres idosas, mesmo após o ajuste do modelo (HR: 2,08, p = 0,038 e HR: 2,68, p = 0,036). Níveis de IL-1β acima da mediana (> 13,4 pg/mL) em mulheres idosas foram associados a risco aumentado para todos os desfechos após o ajuste (todas as causas - HR: 2,03, p = 0,031; DCV - HR: 3,01, p = 0,013; desfecho combinado - HR: 3,05, p = 0,029). Para homens, não foram observadas associações entre Netrina-1 ou IL-1β e os desfechos. Conclusão Níveis séricos elevados de Netrina-1 e IL-1β mostraram associação significativa com pior prognóstico em idosas do sexo feminino. Eles podem ser úteis como indicadores prognósticos em SCA. (Arq Bras Cardiol. 2020; 114(3):507-514)


Abstract Background Several markers have been evaluated for a potential impact on clinical decisions or mortality prediction in acute coronary syndrome (ACS), including Netrin-1 and IL-1β that have been associated with cardiovascular disease. Objective Our study examined the prognostic value of Netrin-1 and IL-1β in patients with ACS (2-year follow-up). Methods We evaluate Netrin-1, IL-1β and other risk factors in the serum sample of 803 patients. Kaplan-Meier curves and Cox regression were used for the analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction (MI) or new non-fatal MI, considering p-value < 0.05. Results There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. Netrin-1 levels above the median (>44.8 pg/mL) were associated with a worse prognosis (all-cause mortality and cardiovascular mortality) in elderly females, even after model adjustment (HR: 2.08, p = 0.038 and HR: 2.68, p = 0.036). IL-1β levels above the median (>13.4 pg/mL) in elderly females were associated with increased risk of all outcomes after adjustment (all-cause mortality - HR: 2.03, p = 0.031; cardiovascular mortality - HR: 3.01, p = 0.013; fatal MI or new non-fatal MI - HR: 3.05, p = 0.029). For males, no associations were observed between Netrin-1 or IL-1β and outcomes. Conclusion High serum levels of Netrin-1 and IL-1β showed significant association with worse prognosis in elderly females. They may be useful as prognostic indicators in ACS. (Arq Bras Cardiol. 2020; 114(3):507-514)


Subject(s)
Humans , Female , Aged , Interleukin-1beta/blood , Acute Coronary Syndrome , Netrin-1/blood , Prognosis , Biomarkers , Risk Factors , Follow-Up Studies , Myocardial Infarction
12.
Braz. j. med. biol. res ; 53(6): e9489, 2020. graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132521

ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune disease of knee joints involving pain and inflammation. Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on complete Freund's adjuvant (CFA)-induced arthritis in the rat model. Treatment with rhoifolin (10 and 20 mg/kg) showed a significant improvement in the overall health parameters such as paw edema and weight loss. This improvement in morphological parameters corroborated the findings with gross morphological changes observed in the histopathological analysis. Rhoifolin treatment also caused a significant decrease in oxidative stress, evident from changes in intracellular levels of glutathione, glutathione peroxidase, malondialdehyde, and superoxide dismutase in the articular cartilage tissue. Moreover, proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin(IL)-1β, and IL-6 showed a significant downregulation of gene expression and intracellular protein concentration levels. The NF-κB pathway showed a significant attenuation as evident in the significant reduction in the levels of NF-κB p65 and p-IκB-α. These results indicated that rhoifolin can be a natural therapeutic alternative to the extant regimens, which include non-steroidal anti-inflammatory drugs and immunosuppressants. Additionally, the antioxidant and anti-inflammatory action of rhoifolin was probably mediated by the NF-κB pathway. However, the exact target molecules of this pathway need to be determined in further studies.


Subject(s)
Animals , Male , Rats , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Flavonoids/administration & dosage , Freund's Adjuvant/administration & dosage , Cytokines/blood , Oxidative Stress/drug effects , Disaccharides/administration & dosage , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/metabolism , Biomarkers/blood , NF-kappa B/drug effects , NF-kappa B/metabolism , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood , Interleukin-1beta/blood , Glycosides/administration & dosage
13.
Braz. j. med. biol. res ; 53(12): e9949, 2020. tab, graf
Article in English | 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
14.
Protein & Cell ; (12): 881-893, 2020.
Article in English | WPRIM | ID: wpr-880884

ABSTRACT

Cytokines are secreted by various cell types and act as critical mediators in many physiological processes, including immune response and tumor progression. Cytokines production is precisely and timely regulated by multiple mechanisms at different levels, ranging from transcriptional to post-transcriptional and posttranslational processes. Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), a potent immunosuppressive protein, was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1 (MCP-1) and subsequently found to possess intrinsic RNase and deubiquitinase activities. MCPIP1 tightly regulates cytokines expression via various functions. Furthermore, cytokines such as interleukin 1 beta (IL-1B) and MCP-1 and inflammatory cytokines inducer lipopolysaccharide (LPS) strongly induce MCPIP1 expression. Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment. In this review, we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.


Subject(s)
Chemokine CCL2/immunology , Humans , Interleukin-1beta/immunology , Neoplasm Proteins/immunology , Neoplasms/pathology , Ribonucleases/immunology , Transcription Factors/immunology
15.
J. appl. oral sci ; 28: e20200033, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1134805

ABSTRACT

Abstract Aim To evaluate the cytotoxicity, biocompatibility and mineralization capacity of BIO-C PULPO, and MTA. Methodology L929 fibroblasts were cultured and MTT assay was used to determine the material cytotoxicity on 6, 24, and 48 h. A total of 30 male rats (Wistar) aged between 4 and 6 months, weighing between 250 and 300 g were used. Polyethylene tubes containing BIO-C PULPO, MTA, and empty tubes were implanted into dorsal connective tissue. After the experimental periods (7, 15, 30, 60, and 90 days) the tubes were histologically analyzed using hematoxylin-eosin (H&E), immunolabeling of IL-1β and TNF-α, and von Kossa staining, or without staining for polarized light analysis. The average number of inflammatory cells was quantified; the mineralization assessment was determined by the area marked in μm2 and semiquantitative immunolabeling analyses of IL-1β and TNF-α were performed. Then, data underwent statistical analysis with a 5% significance level. Results It was observed that BIO-C PULPO and MTA presented cytocompatibility at 6, 24, and 48 similar or higher than control for all evaluated period. On periods 7 and 15 days, BIO-C PULPO was the material with the highest number of inflammatory cells (p<0.05). On periods 30, 60, and 90 days, BIO-C PULPO and MTA presented similar inflammatory reactions (p>0.05). No statistical differences were found between Control, BIO-C PULPO, and MTA for immunolabeling of IL-1β and TNF-α in the different periods of analysis (p<0.05). Positive von Kossa staining and birefringent structures under polarized light were observed in all analyzed periods in contact with both materials, but larger mineralization area was found with BIO-C PULPO on day 90 (p<0.05). Conclusion BIO-C PULPO was biocompatible and induced mineralization similar to MTA.


Subject(s)
Animals , Male , Rats , Root Canal Filling Materials , Tumor Necrosis Factor-alpha/metabolism , Dental Cements , Interleukin-1beta/metabolism , Biomineralization , Oxides , Biocompatible Materials , Rats, Wistar , Silicates , Calcium Compounds , Aluminum Compounds , Subcutaneous Tissue , Drug Combinations , Inflammation
16.
Clinics ; 75: e1868, 2020. graf
Article in English | LILACS | ID: biblio-1142771

ABSTRACT

OBJECTIVES: The present study was designed to explore the roles of inflammatory cytokines interleukin-1β (IL-1β) and Tumor growth factor-β (TGF-β) in the diagnosis and treatment of neonate bilirubin encephalopathy (BE). METHODS: A total of 128 BE neonates and 128 normal neonates were included. The serum samples of the BE children and controls were collected, and the levels of IL-1β and TGF-β were examined. Moreover, the correlation between the level of bilirubin and serum expression of IL-1β or TGF-β in BE patients was analyzed. Finally, receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of the cytokines. RESULTS: IL-1β and TGF-β levels were higher in the serum of BE patients than those in non-BE patients, and the expression of either IL-1β or TGF-β showed a strong positive correlation with the serum expression of bilirubin in BE patients. Moreover, the results of ROC analysis showed that either IL-1β or TGF-β could distinguish BE patients from healthy controls. CONCLUSION: IL-1β and TGF-β levels were upregulated in BE and might function as potential biomarkers or therapeutic targets for BE patients.


Subject(s)
Humans , Infant, Newborn , Child , Cytokines , Kernicterus , Biomarkers , Transforming Growth Factor beta , Tumor Necrosis Factor-alpha , Interleukin-1beta
17.
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
18.
Article in Chinese | WPRIM | ID: wpr-828626

ABSTRACT

OBJECTIVE@#To study whether pyroptosis is involved in the bilirubin-induced injury of primary cultured rat cortical microglial cells.@*METHODS@#Primary cultured rat cortical microglial cells were randomly administered with 30 μmol/L bilirubin (bilirubin group), 30 μmol/L bilirubin following 30 μmol/L VX-765 pretreatment (VX-765+bilirubin group), or an equal volume of dimethyl sulfoxide (control group). Modified MTT assay was used to measure the viability of microglial cells. Western blot was used to measure the expression of the pyroptosis-related proteins Caspase-1 and gasdermin D (GSDMD). Lactate dehydrogenase (LDH)-release assay was used to evaluate the cytotoxicity of microglial cells. EtBr/EthD2 with different molecular weights (394 Da/1 293 Da) was used to measure the size of plasma membrane pores. ELISA was used to measure the level of the inflammatory factor interleukin-1β (IL-1β) in culture supernatant.@*RESULTS@#After bilirubin stimulation, the viability of microglial cells decreased and LDH release increased, both in a time-dependent manner. Compared with the control group, the bilirubin group had a significantly higher positive rate of small-molecule EtBr passing through the cell membrane (P0.05). The expression of activated Caspase-1 significantly increased at 0.5 hour after bilirubin stimulation (P<0.05), and that of activated GSDMD significantly increased at 6 hours after bilirubin stimulation (P<0.05). The release of IL-1β significantly increased at 6 hours after bilirubin stimulation and reached the peak at 24 hours (P<0.001). Compared with the bilirubin group, the VX-765+bilirubin group had a significant increase in cell viability (P<0.05) and significant reductions in the expression of activated GSDMD, the pass rate of EtBr, and the release of LDH and IL-1β (P<0.05).@*CONCLUSIONS@#Pyroptosis is involved in bilirubin-induced injury of primary cultured microglial cells.


Subject(s)
Animals , Bilirubin , Caspase 1 , Cell Survival , Interleukin-1beta , Pyroptosis , Rats
19.
Article in Chinese | WPRIM | ID: wpr-828285

ABSTRACT

Knee osteoarthritis is the most common type of arthritis, which is manifested by the deformation and degeneration of articular cartilage and the discomfort of patients with joint pain, which affects the quality of life of patients and aggravates the medical burden of society. The pathogenesis of knee osteoarthritis is very complex. This paper reviews the inflammatory factors and signal pathways involved in knee osteoarthritis. It is found that most of the inflammatory factors involved are interleukin, such as IL-1 β, IL-6, IL-15, IL-17, IL-18, and tumor necrosis factors, such as TNF-α. These inflammatory factors aggravate knee osteoarthritisby activating corresponding pathways and promoting the release of inflammatory mediators. The inflammatory signaling pathways involved in knee osteoarthritis are complex. Notch pathway, Wnt pathway, SDF-1 / CXCR4 pathway, TLRs pathway, MAPKs pathway, hippo Yap pathway, OPG-RANK-RANKL pathway and TGF-β pathway are all involved in the regulation of knee osteoarthritis, and the pathways related to inflammatory mechanism are mainly MAPKs pathway and TLRs pathway. Different signaling pathways can cause the destruction of articular cartilage, promote the apoptosis of chondrocytes, and finally lead to the further imbalance of homeostasis in the knee joint. At the same time, the activation of signal pathway can promote the release of inflammatory factors, so under the cascade reaction of inflammatory factors and signal pathway, knee osteoarthritis is aggravating.


Subject(s)
Cartilage, Articular , Chondrocytes , Humans , Interleukin-1beta , Osteoarthritis, Knee , Quality of Life , Signal Transduction
20.
Article in Chinese | WPRIM | ID: wpr-826680

ABSTRACT

OBJECTIVE@#To observe the effects of electroacupuncture (EA) pretreatment on the cardiac ejection fraction (EF), the number of macrophages in spleen and heart, and the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and interleukin-1β (IL-1β) in myocardium in mice with acute myocardial ischemia, and to explore the possible mechanism of EA pretreatment on promoting myocardial protection.@*METHODS@#A total of 30 male C57BL/6J mice were randomly divided into a control group, a model group and an EA pretreatment group, 10 rats in each group. The acute myocardial ischemia model was established by ligating the left anterior descending branch of the coronary artery in the model group and EA pretreatment group, while threading but no ligating at left anterior descending branch of the coronary artery was applied in the control group. In the EA pretreatment group, mice were intervented with EA at bilateral "Neiguan" (PC 6), disperse-dense wave, frequency of 2 Hz/15 Hz, intensity of 2 mA; each EA treatment last for 20 min, once a day, and 3-day treatment was given before model establishment. The EF value was evaluated by ultrasonic cardiogram; the number of macrophages in spleen and heart was measured by flow cytometry; the expression level of NLRP3 and IL-1β in myocardium was measured by Western blot.@*RESULTS@#Compared with the control group, the EF value was decreased in the model group (<0.001), the number of macrophages in the heart and spleen was increased (<0.001), and the expression level of NLRP3 and IL-1β in the myocardium was increased (<0.001, <0.01). Compared with the model group, the EF value was increased in the EA pretreatment group (<0.01), the number of macrophages in the heart and spleen was decreased (<0.01), and the expression level of NLRP3 and IL-1β in the myocardium was decreased (<0.01, <0.05).@*CONCLUSION@#EA pretreatment could reduce the number of macrophages in spleen and heart, down-regulate the expression of NLRP3 and IL-1β in myocardial tissue in mice with acute myocardial ischemia, which could relieve the local inflammatory response and achieve the myocardial protective effect.


Subject(s)
Acupuncture Points , Animals , Electroacupuncture , Heart , Physiology , Inflammation , Allergy and Immunology , Interleukin-1beta , Metabolism , Macrophages , Cell Biology , Male , Mice , Mice, Inbred C57BL , Myocardial Ischemia , Allergy and Immunology , Therapeutics , Myocardium , NLR Family, Pyrin Domain-Containing 3 Protein , Metabolism , Random Allocation , Spleen
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