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1.
Ann Hematol ; 99(2): 359-361, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872359
2.
Immunity ; 51(6): 983-996.e6, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31836429

RESUMO

Excessive activation of the coagulation system leads to life-threatening disseminated intravascular coagulation (DIC). Here, we examined the mechanisms underlying the activation of coagulation by lipopolysaccharide (LPS), the major cell-wall component of Gram-negative bacteria. We found that caspase-11, a cytosolic LPS receptor, activated the coagulation cascade. Caspase-11 enhanced the activation of tissue factor (TF), an initiator of coagulation, through triggering the formation of gasdermin D (GSDMD) pores and subsequent phosphatidylserine exposure, in a manner independent of cell death. GSDMD pores mediated calcium influx, which induced phosphatidylserine exposure through transmembrane protein 16F, a calcium-dependent phospholipid scramblase. Deletion of Casp11, ablation of Gsdmd, or neutralization of phosphatidylserine or TF prevented LPS-induced DIC. In septic patients, plasma concentrations of interleukin (IL)-1α and IL-1ß, biomarkers of GSDMD activation, correlated with phosphatidylserine exposure in peripheral leukocytes and DIC scores. Our findings mechanistically link immune recognition of LPS to coagulation, with implications for the treatment of DIC.


Assuntos
Caspases Iniciadoras/metabolismo , Coagulação Intravascular Disseminada/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipopolissacarídeos/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Fosfatidilserinas/metabolismo , Tromboplastina/metabolismo , Animais , Coagulação Sanguínea/fisiologia , Caspases Iniciadoras/genética , Linhagem Celular Tumoral , Endotoxemia/patologia , Ativação Enzimática , Células HT29 , Células HeLa , Humanos , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Ligação a Fosfato/genética , Piroptose/fisiologia , Transdução de Sinais/fisiologia
3.
Georgian Med News ; (294): 68-71, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687952

RESUMO

The aim of our work was to determine the gene polymorphism of cytokines IL-1ß (-511) and IL-10 (-1082) in children with nephrotic syndrome. 20 patients with nephrotic syndrome were recruited into the study from 2017 to 2018 years in single center. Our study included children with levels of glomerular filtration rate >90 ml/min. Genetic polymorphism of IL-1ß (-511) and IL-10 (-1082) and serum IL1ß were evaluated. Analyzing the contents of IL-1ß in serum of children with nephrotic syndrome, we found that IL-1ß was significantly increased in children with steroid-resistant nephrotic syndrome and with progression of glomerulonephritis compared with remission and with healthy children (p<0.05). The presence of C/T genotype is associated with increased production of interleukin-1ß in serum, compared with children with genotype C/C (p<0.05). Checking the polymorphism of SNP -1082 of IL-10 we determined that in 50% of children with nephrotic syndrome there was G/A genotype, in 40% - G/G genotype, and genotype А/А was only in 10% of patients. A strong direct relationship between the level of IL-1ß in serum and C/T allelic polymorphism of the gene IL-1ß (-511) was found (r=+0,56) (p<0.05). Gene polymorphism of IL-1ß (-511) can be used as a marker of progression of glomerulonephritis, nephrotic syndrome but more studies are needed.


Assuntos
Interleucina-10/genética , Interleucina-1beta/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Polimorfismo Genético/genética , Criança , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Masculino , Síndrome Nefrótica/imunologia
4.
Medicine (Baltimore) ; 98(42): e17416, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626097

RESUMO

This study aims to evaluate the clinical value of haptoglobin (Hp) and sCD163 testing for the differential diagnosis of pleural effusion, and investigate the correlation of Hp and sCD163 with the inflammatory response of the body.Pleural effusion samples were collected from 78 patients (38 tuberculous pleural effusions [TPE] and 40 malignant pleural effusions [MPE]). The concentrations of Hp and sCD163 in the pleural effusion were measured by enzyme-linked immunosorbent assay (ELISA).The concentrations of Hp and sCD163 were significantly higher in the TPE group than in the MPE group (P < .05). The sensitivity and specificity of the Hp test for the differential diagnosis of TPE and MPE was 82.4% and 86.1%, respectively (P < .01), while the cut off value was 779.05 ug/mL. Furthermore, the sensitivity and specificity of the sCD163 test for the differential diagnosis of TPE and MPE was 76.3% and 85.0%, respectively (P < .01), while the cut off value was 16,401.11 ng/mL. Moreover, the sensitivity and specificity of the combination of Hp and sCD163 tests for diagnosing TPE was 90.0% and 87.5%, respectively. Hp and IL-1ß, TNF-α, CRP and ESR were positively correlated in both the TPE group and MPE group (P < .05). Hp and sCD163 were positively correlated in the TPE group (r = 0.3735, P = .0209), but not in the MPE group (r = 0.22, P = .1684). However, there was no correlation between sCD163 and TNF-α, CRP and ESR in either the TPE group, or the MPE group (P > .05). Furthermore, sCD163 and IL-1ß were weakly correlated in the TPE group (r = 0.49, P = .0018), but these had no correlation in the MPE group (r = 0.068, P = .6767).Hp and sCD163 can be used as biological markers for the differential diagnosis of pleural effusion in clinic, and the level of Hp in pleural effusion may reflect the intensity of inflammation in the body to some extent.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Haptoglobinas/análise , Derrame Pleural Maligno/diagnóstico , Receptores de Superfície Celular/sangue , Tuberculose/diagnóstico , Idoso , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/sangue , Curva ROC , Sensibilidade e Especificidade , Fator de Necrose Tumoral alfa/sangue
5.
Rev Assoc Med Bras (1992) ; 65(9): 1188-1192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618336

RESUMO

OBJECTIVE: We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1ß) in pentylenetetrazol-induced seizures in rats. METHODS: Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1ß concentrations were measured using ELISA. RESULTS: Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1ß concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1ß concentrations. However, obestatin did not change CGRP, SP, and IL-1ß concentrations. CONCLUSION: Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.


Assuntos
Convulsivantes/efeitos adversos , Neuropeptídeos/efeitos dos fármacos , Pentilenotetrazol/efeitos adversos , Hormônios Peptídicos/farmacologia , Convulsões/induzido quimicamente , Animais , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina/efeitos dos fármacos , Modelos Animais de Doenças , Grelina/farmacologia , Inflamação , Interleucina-1beta/sangue , Interleucina-1beta/efeitos dos fármacos , Masculino , Mioclonia , Distribuição Aleatória , Ratos Wistar , Convulsões/metabolismo , Substância P/sangue , Substância P/efeitos dos fármacos , Fatores de Tempo , Peptídeo Intestinal Vasoativo/farmacologia
6.
Artigo em Chinês | MEDLINE | ID: mdl-31495108

RESUMO

Objective: To investigate the protective effect of oligomeric proanthocyanidins (OPCs) in paraquat-exposed mice. Methods: An acute lung injury model was established by a single intraperitoneal injection of paraquat (PQ) in BALB/c mice. The mice were randomized into control group, paraquat-exposed group (PQ group) , oligomeric proanthocyanidins group (OPCs group) , and paraquat and oligomeric proanthocyanidins-exposed group (PQ+OPCs group) , with 10 mice in each group. Only normal saline was intraperitoneally injected into the mice in the control group. The mice in the PQ group were divided into 8 subgroups according to the dose of poison administered, i.e., 0, 25, 50, 75, 100, 150, 200, and 300 mg/kg; the mice in each subgroup were given a single intraperitoneal injection of PQ and were observed and recorded for death at 3, 6, 12, 24, 36, 48, 60, 84, and 96 hours after PQ injection. Origin 8.0 was used to calculate the median lethal dose (LD(50)) of the mice at 24, 36, 48, and 60 hours after PQ injection, and the PQ dose (100 mg/kg, ip) was chosen based on the accumulated mortality rate. An OPCs-treated experimental model was established by an intraperitoneal injection of OPCs followed by a single PQ injection (100 mg/kg, ip) 1 hour later to observe the effects of OPCs on the apparent poisoning effect and fatality rate in PQ-induced mice. Immunohistochemistry was used to determine the effect of OPCs on PQ-induced lung tissue lesions. The peripheral blood samples of the mice were collected to determine the effects of OPCs on PQ-induced inflammatory factors such as tumor necrosis factor-α (TNF-α) , interleukine-1ß (IL-1ß) , and transforming growth factor-ß1 (TGF-ß1) using enzyme-linked immunosorbent assay. Results: The mortality rate was significantly correlated with the dose and exposure time in PQ-exposed mice; the mortality rate gradually increased with increasing dose and exposure time of the poison (P<0.05) . The LD(50) values for the mice were 216.67, 124.11, and 71.24 mg/kg at 24, 48, and 72 hours after PQ exposure, respectively. PQ could induce animal death at 12 hours after injection, and the mortality rate of the animals was 40% (4/10) at 48 hours after PQ exposure. The PQ-induced mortality rate of the mice in the PQ+OPCs group was reduced, and the mortality rate of the animals was 10% (1/10) at 48 hours after PQ exposure. Compared with treatment in the control group, OPCs exposure alone had no significant effect on the expression of TNF-α and TGF-ß1 in the peripheral blood (P>0.05) , but it significantly inhibited the expression of IL-1ß (P<0.05) . After 48 hours, the expression of TNF-α, TGF-ß1, and IL-1ß in peripheral blood significantly increased by 39%, 45%, and 38%, respectively, in the PQ group (P<0.05) , but they significantly decreased by 31%, 13%, and 22%, respectively, in the OPCs+PQ group as compared with the PQ group (P<0.05) . Conclusion: OPCs pretreatment can significantly alleviate PQ-induced poisoning effect.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Paraquat/toxicidade , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Interleucina-1beta/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Fator de Crescimento Transformador beta1/sangue , Fator de Necrose Tumoral alfa/sangue
7.
J Dairy Sci ; 102(11): 10554-10563, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495623

RESUMO

Ketosis is an important metabolic disease that can negatively affect the production efficiency of dairy cows. Earlier studies have revealed metabolic and inflammatory alterations in the blood associated with ketosis; however, a link between ketosis and hepatic inflammation has not been well documented. The objective of this study was to investigate whether the nuclear factor kappa B (NF-κB) signaling pathway and NLR family pyrin domain containing 3 (NLRP3) inflammasome were activated in the liver of ketotic cows. Liver and blood samples were collected from healthy (n = 15, control group) and ketotic (n = 15, ketosis group) cows that had a similar number of lactations (median = 3, range = 2 to 4) and days in milk (median = 6 d, range = 3 to 9 d). Results showed that serum levels of fatty acids, ß-hydroxybutyrate (BHB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were higher and glucose was lower in ketotic cows. Concentrations of serum proinflammatory cytokines IL18, tumor necrosis factor (TNF)-α, and IL1B were greater and the anti-inflammatory cytokine IL10 was lower in the ketosis group. Cows with ketosis had triacylglycerol accumulation in the liver. Upregulation of phosphorylated (p)-NF-κB and p-inhibitor of κB (IκB)α protein abundance in cows with ketosis indicated that the hepatic NF-κB signaling pathway was overactivated. The mRNA abundance of TNFA, inducible nitric oxide synthase (NOS2), IL18, and IL1B were greater and IL10 was lower in ketotic cows. More importantly, the mRNA and protein abundance of NLRP3 and caspase-1 (CASP1) along with CASP1 activity were greater in the liver of cows with ketosis. Overall, the data indicate that the onset of ketosis is accompanied by activation of the NF-κB signaling pathway and NLRP3 inflammasome, resulting in a state of inflammation.


Assuntos
Doenças dos Bovinos/metabolismo , Inflamassomos/metabolismo , Cetose/veterinária , Fígado/metabolismo , NF-kappa B/metabolismo , Domínio Pirina/fisiologia , Ácido 3-Hidroxibutírico/sangue , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Bovinos , Doenças dos Bovinos/sangue , Citocinas/sangue , Ácidos Graxos/sangue , Feminino , Inflamação , Interleucina-10/sangue , Interleucina-1beta/sangue , Cetose/metabolismo , Lactação , Leite/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/sangue , Regulação para Cima
8.
Mol Cell Biochem ; 462(1-2): 123-132, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31446615

RESUMO

Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute renal failure. After IR, the inflammatory and apoptotic process is triggered. The relation of Cannabinoid type 2 (CB2) receptor with inflammatory and apoptotic process has been determined. The CB2 receptor has been shown to be localized in glomeruli and tubules in human and rat kidney. Activation of CB2 receptor with JWH-133 has been shown to reduce apoptosis and inflammation. In this study, it was investigated whether CB2 activation with selective CB2 receptor agonist JWH-133 was protective against renal IR injury. Male Sprague-Dawley rats were divided into 5 groups (n = 45). Bilateral ischemia was treated to the IR group rat's kidneys for 45 min and then reperfusion was performed for 24 h. Three different doses of JWH-133 (0.2, 1 and 5 mg/kg) were administered to the treatment groups at the onset of ischemia. The JWH-133 application at three different doses decreased the glomerular and tubular damage. Additionally, in the renal tissue, nuclear factor-κB, tumour necrosis factor alpha, interleukin-1beta, and caspase-3 levels decreased immunohistochemically. Similarly, JWH-133 application decreased the serum tumour necrosis factor alpha, blood urea nitrogen, creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, Cystatin C, interleukin-18, interleukin-1beta, interleukin-6, and interleukin-10 levels. We found that JWH-133 and CB2 receptor activation had a curative effect against kidney IR damage. JWH-133 may be a new therapeutic agent in preventing kidney IR damage.


Assuntos
Rim/patologia , Substâncias Protetoras/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteínas da Fase Aguda/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Canabinoides/administração & dosagem , Canabinoides/farmacologia , Caspase 3/metabolismo , Creatinina/sangue , Cistatina C/sangue , Interleucina-10/sangue , Interleucina-18/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Lipocalinas/metabolismo , Masculino , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/sangue
9.
Int J Sports Med ; 40(12): 762-767, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31466082

RESUMO

This study compared internal load variable dynamics across three consecutive football matches and investigated its relationship with the number of sprints performed by players. Twenty-three male players had blood and salivary samples collected for hormonal concentration (testosterone, cortisol, and testosterone-cortisol ratio), and serum analysis (interleukin-6, interleukin-1-beta, and c-reactive-protein), respectively. Sprints were measured through Global Position System devices. Testosterone and testosterone-cortisol-ratio presented a decreasing behavior up to the second match, and all other indicators presented an increasing behavior during the same period, c-reactive-protein was the only indicator observed to significantly rise up to the third match as well (0.38±0.02 mg/L; 0.49±0.05 mg/L; 0.69±0.05 mg/L; 0.89±0.08 mg/L). C-reactive-protein showed strong correlations with sprints in the second and third matches (p<0.01, r=0.71 and 0.79), and weak-to-moderate in the first one (p<0.05, r=0.59). Interleukin-6 and interleukin-1-beta presented weak-to-moderate correlation in every match (p<0.05, r=0.48 to 0.51; r=0.51 to 0.55) while testosterone-cortisol ratio presented weak-to-moderate correlation only in the third one (p<0.05, r=0.42). Multilevel linear regression showed that c-reactive-protein had a higher R2 than other biomarker in any regression model (R2=0.624; p<0.001). Therefore, c-reactive-protein can be a valid and reliable indicator of sprinting in competitive football. Future research should explore longer periods of monitoring and/or others external load variables so that other behaviors may arise to knowledge.


Assuntos
Proteína C-Reativa/metabolismo , Comportamento Competitivo/fisiologia , Corrida/fisiologia , Futebol/fisiologia , Adolescente , Biomarcadores/sangue , Biomarcadores/metabolismo , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Interleucina-1beta/sangue , Masculino , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Receptores de Interleucina-6/sangue , Saliva/metabolismo , Testosterona/sangue , Testosterona/metabolismo , Adulto Jovem
10.
Bioelectrochemistry ; 130: 107287, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31400567

RESUMO

This work reports the first electrochemical molecularly imprinted polymer (MIP) sensor for Interleukin-1beta (IL-1ß) detection, based on modified commercial screen-printed carbon electrode (SPCE) was successfully demonstrated. For this purpose, the carbon support was modified with a PEDOT/4-aminothiophenol layer prior to the MIP film to enhance sensitivity and signal stability. The MIP layer was constructed on top of this by electropolymerization of Eriochrome black T (EBT) in the presence of IL-1ß. The several steps of the biosensor assembly was followed by Raman spectroscopy and electroanalytical techniques. Using electrochemical impedance spectroscopy (EIS), a linear response in the range of 60 pM to 600 nM, with a LOD of 1.5 pM with (S/N = 3) was obtained in neutral PBS. Selectivity tests of the MIP biosensor made in spiked synthetic serum samples as well as against other structurally related (Myoglobin, of similar shape and size) or competing compounds (Immunoglobulin G, also present in the human serum) confirmed the good selectivity of the biosensor. Overall, the biosensor described herein has the potential to provide a simple and quick way for on-site screening of IL-1ß, with low sample/reagent consumption and enabling direct serum analysis, which constitutes a valuable alternative to other conventional methods.


Assuntos
Técnicas Biossensoriais/métodos , Interleucina-1beta/sangue , Impressão Molecular/métodos , Compostos Azo/química , Técnicas Biossensoriais/instrumentação , Carbono/química , Espectroscopia Dielétrica/instrumentação , Espectroscopia Dielétrica/métodos , Eletrodos , Desenho de Equipamento , Humanos , Interleucina-1beta/análise , Impressão Molecular/instrumentação , Polimerização , Polímeros/química
11.
Int Arch Allergy Immunol ; 180(2): 79-90, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31340215

RESUMO

BACKGROUND: In this study, we examined whether RORA (retinoic acid receptor-related orphan receptor alpha) was capable of alleviating the progression of allergic rhinitis (AR). METHODS: In order to elucidate the possible effects of RORA and the regulatory mechanism between RORA and the Wnt/ß-catenin signaling pathway, mouse AR models were established and treated with RORA vector, siRNA against RORA, or the Wnt/ß-catenin pathway inhibitor WIF-1. Subsequently, the serum levels of inflammatory cytokines (IgE, INF-γ, IL-1ß, IL-4, and IL-17), red blood cell (RBC) immune adhesion function, the levels of RORA, ß-catenin, and GSK3ß, as well as the extent of ß-catenin and GSK-3ß phosphorylation were evaluated and measured. RESULTS: The OVA-induced AR mouse model exhibited obvious nasal mucosal injury and inflammatory cell infiltration. RORA overexpression or the inactivation of the Wnt/ß-catenin signaling pathway was uncovered as a way to ameliorate nasal mucosal injury and eosinophil infiltration of the OVA-induced AR mouse model. On the other hand, it reduced the number of eosinophils and mast cells, which also resulted in downregulated expression of IgE, INF-γ, IL-1ß, IL-4, IL-17, ß-catenin, and GSK-3ß. Moreover, this led to a decreased extent of ß-catenin and GSK-3ß phosphorylation, while the rates of C3b receptor rosette and Ic rosette were elevated. CONCLUSION: Taken together, the key findings provided evidence suggesting that the elevated RORA could potentially alleviate nasal mucosal injury and simultaneously enhance RBC immune adhesion function through the inhibition of the Wnt/ß-catenin signaling pathway activation in an OVA-induced AR mouse model. This emphasizes a novel therapeutic target for the treatment of AR.


Assuntos
Eritrócitos/imunologia , Mucosa Nasal/lesões , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Rinite Alérgica/imunologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Adesão Celular/fisiologia , Modelos Animais de Doenças , Eosinófilos/imunologia , Proteínas da Matriz Extracelular/metabolismo , Reação de Imunoaderência , Imunoglobulina E/sangue , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-1beta/sangue , Interleucina-4/sangue , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Interferência de RNA , RNA Citoplasmático Pequeno/genética , Rinite Alérgica/prevenção & controle , Via de Sinalização Wnt , beta Catenina/sangue
12.
Bull Exp Biol Med ; 167(3): 367-370, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31346882

RESUMO

We analyzed cytokine profile in the sera of CBA mice in 1, 5, and 24 h after intraperitoneal injection of supernatants of broth cultures of group A Streptococcus types 1M and 3M and Dochez NY5 type 10M strain. The increase of the cytokine content was observed in response to supernatants of all three types, but the highest values were recorded after injection of supernatant of strain Dochez-NY5. The level of IL-2 increased most drastically (by 51 times) and the level of IL-5 increased by 8.9 times in comparison with the control. The level of IL-2 also increased after injection of supernatants of type 1M and type 3M, but to a lesser extent (by 5 and 2.3 times, respectively). The content of proinflammatory cytokines IL-1ß, TNFα, and IFNγ in mouse sera increased to a lesser extent than IL-2 after administration of all three supernatants.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Citocinas/sangue , Streptococcus pyogenes/metabolismo , Animais , Interferon gama/sangue , Interleucina-1beta/sangue , Interleucina-2/sangue , Interleucina-5/sangue , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Masculino , Camundongos , Camundongos Endogâmicos CBA
13.
Int Immunopharmacol ; 74: 105625, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302451

RESUMO

Acetaminophen (APAP) is a widely used over-the-counter drug for antipyretic and analgesic, but an overdose will induce acute liver injury. APAP hepatotoxicity has been the most common cause of acute liver failure in western countries with high morbidity and mortality. Geniposide (GP), an iridoid glycoside extracted from the fruit of Gardenia jasminoides, has been reported to exert a profound anti-inflammatory activity on acute and chronic diseases. However, it is never demonstrated whether GP can protect hepatocytes from APAP hepatotoxicity. In this study, we investigated the protective effect and underlying mechanism of GP against AILI. The results showed that GP pretreatment reduced the levels of ALT and AST in a dose-dependent manner and alleviated hepatocyte necrosis and apoptosis in mice exposed at APAP. Moreover, it suppressed the expression of CYP 2E1 and attenuated the exhaustion of GSH and accumulation of MDA in the liver. Furthermore, GP remarkably inhibited inflammatory cells infiltration and mitigated the release of IL-1ß and TNF-α, and inhibited Toll-like receptor 4 (TLR4) expression and nuclear factor kappa (NF-κB) activation. These data suggested that GP could effectively protect hepatocytes from APAP hepatotoxicity through the down-regulation of CYP 2E1 expression and the inhibition of TLR4/NF-κB signaling pathway.


Assuntos
Hepatócitos/efeitos dos fármacos , Iridoides/farmacologia , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Receptor 4 Toll-Like/metabolismo , Acetaminofen , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Regulação para Baixo/efeitos dos fármacos , Glutationa/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Interleucina-1beta/sangue , Iridoides/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
14.
BMC Immunol ; 20(1): 23, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272370

RESUMO

BACKGROUND: Proinflammatory genes are highly expressed in several metabolic disorders associated with obesity. But it is not clarified whether gene expression levels and downstream inflammatory markers are related to the metabolic state or the presence of obesity. Hence, the present study aimed to compare Toll-Like Receptor 2 (TLR2), Myeloid Differentiation Factor 88 (MyD88), and NFĸB mRNA expression levels between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. RESULTS: We compared mRNA expression levels of the genes as well as serum FFAs and IL-1ß in MUAO (n = 36) and MHAO (n = 34) groups. Serum FBS, TG, and HDL-C in addition to systolic and diastolic blood pressure were significantly higher in MUAO than MHAO groups (p < 0.05). The odds of MUAO was significantly decreased with high HDL-C (OR = 0.22, 95%CI: 0.08-0.63) and increased with high FBS (OR = 7.04, 95%CI: 1.42-34.69) and TG (OR = 30.55, 95%CI: 7.48-60.67). There were no significant differences in proinflammatory genes as well as serum FFAs and IL-1ß between the two groups. No associations were found between the genes expression and serum markers. However, NFĸB expression was significantly correlated with TLR2 and MyD88 (r = 0.747; p < 0.001). Significant correlations were also noticed between TLR2 and MyD88 expression as well as between serum FFAs and IL-1ß in each group (p < 0.001). CONCLUSION: Serum concentration of IL-1ß, FFAs, and mRNA expression levels of TLR2, MyD88, and NFĸB may be resulted from abdominal obesity and not be related to the presence or absence of metabolic health.


Assuntos
Ácidos Graxos não Esterificados/sangue , Interleucina-1beta/sangue , Doenças Metabólicas/imunologia , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/genética , Obesidade Abdominal/imunologia , Receptor 2 Toll-Like/genética , Adulto , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Inflamação/genética , Masculino , RNA Mensageiro/genética
15.
Food Funct ; 10(7): 4315-4329, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31271400

RESUMO

In this study, the immunostimulatory activity of Caulerpa lentillifera polysaccharides (CLP) was elucidated in cytoxan (CTX)-induced immunosuppressed BALB/c mice. The results showed that CLP ameliorated the CTX-evoked damage to body weight, colon length and thymus/spleen indexes and enhanced the secretions of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and superoxidase dismutase (SOD) in serum and thymic, splenic and colonic tissues of the immunosuppressed mice. Besides, CLP promoted the production of secretory immunoglobulin A (SIgA) and mucin2 in the colonic tissue of the immunosuppressed mice. Associated with the above immunostimulatory effects, CLP positively affected the production of short chain fatty acids (SCFAs) and microbiota diversity and composition, such as improvement in the growth of Lactobacillus, Coriobacteriaceae, Ruminococcaceae, Clostridium_XVIII and Helicobacter, whereas it suppressed the microbial populations of Bacteroides, Barnesiella and Lachnospiraceae. These findings suggested that CLP modulated SCFA production and gut microbiota in the immunosuppressed mice, evoking the colonic mucosal immunity, which might activate the systemic immunity in blood, thymus and spleen. The results could be helpful for understanding the functions of CLP, supporting their potential as novel prebiotics and immunostimulators.


Assuntos
Adjuvantes Imunológicos/farmacologia , Caulerpa/química , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/sangue , Animais , Biodiversidade , Colo/efeitos dos fármacos , Ciclofosfamida/farmacologia , Ácidos Graxos Voláteis , Imunidade nas Mucosas , Imunoglobulina A Secretora , Interleucina-1beta/sangue , Lactobacillus , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Mucina-2 , RNA Mensageiro/metabolismo , Baço , Timo , Fator de Necrose Tumoral alfa/sangue
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(3): 283-290, 2019 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-31282320

RESUMO

Objective To investigate the effects of simvastatin on diabetic neuropathic pain and systematic inflammation in diabetic rats and explore their molecular mechanisms.Methods Totally 24 rats were equally randomized into the normal+vehicle(NV)group,diabetic+vehicle(DV)group,and diabetic+simvastatin(DS)group using the random number table.Streptozotocin(STZ)was used to establish the rat models of diabetes.Blood glucose,body mass,paw withdrawal mechanical threshold(PWMT),and paw withdrawal thermal latency(PWTL)in each group were observed on days 7,14,21,and 28 after STZ injection.On day 28 after STZ injection,rats were sacrificed,and the lumbar spinal dorsal horn and serum were collected.Western blotting was used to detect the expression of receptor for advanced glycation end products(RAGE)and the phosphorylation levels of protein kinase B(AKT),extracellular signal-regulated kinase(ERK),p38,and c-Jun N-terminal kinase(JNK)in the spinal dorsal horn of rats in each group.Enzyme-linked immunosorbent assay was performed to determine the serum concentrations of oxidized low density lipoprotein(ox-LDL)and interleukin-1ß(IL-1ß).Results On days 14,21 and 28 after STZ injection,the PWMT in DV group were(8.6 ± 0.8),(7.1 ± 1.6),and(7.8 ± 0.8)g respectively,which were significantly lower than (12.0 ± 0.9)(q=8.482,P =0.000),(11.6 ± 1.5)(q=11.309,P =0.000),and(11.7 ± 1.5)g(q=9.801,P =0.000)in NV group.The PWMT in DS group on days 21 and 28 were(9.4 ± 1.4)(q=5.780,P =0.000)and(9.7 ± 0.9)g(q=4.775,P =0.003),respectively,which were significantly improved comparing with those of DV group.On days 7,14,21,and 28,there were no significant differences in PWTL among these three groups (all P<0.05).The expression of RAGE in the spinal dorsal horn of DV group was significantly higher than those of NV group(q=6.299,P =0.000)and DS group(q=2.891,P =0.025).The phosphorylation level of AKT in the spinal dorsal horn of DV group was significantly higher than those of NV group(q=8.915,P=0.000)and DS group(q=4.103,P=0.003).The phosphorylation levels of ERK(q =8.313,P=0.000),p38(q =2.965,P =0.022),and JNK(q=7.459,P =0.000)in the spinal dorsal horn of DV group were significantly higher than those of NV group;the phosphorylation level of JNK in the spinal dorsal horn of DS group was significant lower than that of DV group(q=3.866,P =0.004);however,there were no significant differences in the phosphorylation levels of ERK(q=1.987,P=0.122)and p38(q=1.260,P=0.375)in the spinal dorsal horn between DS group and DV group.The serum concentrations of ox-LDL and IL-1ß in DV group were(41.86 ± 13.40)ng/ml and(108.16 ± 25.88)pg/ml,respectively,which were significantly higher than those in NV group [(24.66 ± 7.87)ng/ml(q=3.606,P=0.003)and(49.32 ± 28.35)pg/ml(q=5.079,P=0.000)] and DS group [(18.81 ± 5.62)ng/ml (q=4.833,P =0.000)and(32.73 ± 11.73)pg/ml(q=6.510,P =0.000)].Conclusions Simvastatin can relieve the mechanical allodynia of diabetic rats possibly by inhibiting the activation of RAGE/AKT and the phosphorylation of JNK in the spinal dorsal horn.Simvastatin can also decrease the serum concentrations of ox-LDL and IL-1ß in diabetic rats,which may contribute to the relief of systematic inflammation.


Assuntos
Diabetes Mellitus Experimental/complicações , Inflamação/tratamento farmacológico , Neuralgia/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Hiperalgesia , Interleucina-1beta/sangue , Lipoproteínas LDL/sangue , Proteínas Proto-Oncogênicas c-akt/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada/metabolismo
17.
Exp Oncol ; 41(2): 112-122, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31262159

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is an anticancer therapy that associates the photosensitizer (PS), oxygen and light to destroy cancer cells. Methylene blue (MB) is considered a second generation phenothiazine dye with excellent photochemical properties. AIM: To evaluate whether MB-mediated PDT can induce oxidative stress and inflammation, therefore, interfering tumor growth. MATERIALS AND METHODS: The study was conducted on Wistar rats transplanted with Walker 256 carcinosarcoma (W256). The proinflammatory interleukins levels (IL-1ß, IL-6, IL-10, TNF-α) were determined by ELISA, mRNA expression of COX-1, COX-2, iNOS and eNOS by RT-PCR, lipid peroxidation was measured by the TBARS method. Moreover, myeloperoxidase (MPO) activity in neutrophils was determined by MPO activity assay. All indices mentioned above were determined in tumor tissue. Kaplan - Meier and Gehan - Breslow - Wilcoxon tests were used for survival analysis. RESULTS: We found that the treatment of W256 with 0.1% MB + 1 J/cm2 provoked a significant increase in the interleukins levels (IL-1ß, IL-6, IL-10, TNF-α), prostaglandin E2, the mRNA expression of COX-2, iNOS, lipid peroxidation and MPO activity in tumor tissue, which were statistically different (p < 0.05) compared to other experimental and control groups. The results of the estimation of survival curves show a greater probability of survival in 0.1% MB + 1 J/cm2 (total energy dose =142.8 J/cm2) treated group. CONCLUSION: Our results suggest that treatment of W256 with 0.1% MB + 1 J/cm2 was able to promote cytotoxic effects in tumor tissue by the generation of reactive oxygen species causing inflammation and thus interfering in the tumor growth.


Assuntos
Carcinoma 256 de Walker/tratamento farmacológico , Azul de Metileno/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Proteínas de Transporte/sangue , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Feminino , Inflamação/induzido quimicamente , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Peroxidação de Lipídeos , Proteínas de Membrana/metabolismo , Neutrófilos/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
18.
EBioMedicine ; 45: 278-289, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31257148

RESUMO

BACKGROUND: Leukocyte-associated immunoglobulin like receptor-1 (LAIR1) is a transmembrane inhibitory receptor that influences susceptibility to a myriad of inflammatory diseases. Our recent investigations of severe malarial anaemia (SMA) pathogenesis in Kenyan children discovered that novel LAIR1 genetic variants which were associated with decreased LAIR1 transcripts enhanced the longitudinal risk of SMA and all-cause mortality. METHODS: To characterize the molecular mechanism(s) responsible for altered LAIR1 signalling in severe malaria, we determined LAIR1 transcripts and protein, sLAIR1, sLAIR2, and complement component 1q (C1q) in children with malarial anaemia, followed by a series of in vitro experiments investigating the LAIR1 signalling cascade. FINDINGS: Kenyan children with SMA had elevated circulating levels of soluble LAIR1 (sLAIR1) relative to non-SMA (1.69-fold P < .0001). The LAIR1 antagonist, sLAIR2, was also elevated in the circulation of children with SMA (1.59 fold-change, P < .0001). There was a positive correlation between sLAIR1 and sLAIR2 (ρ = 0.741, P < .0001). Conversely, circulating levels of complement component 1q (C1q), a LAIR1 natural ligand, were lower in SMA (-1.21-fold P = .048). These in vivo findings suggest that reduced membrane-bound LAIR1 expression in SMA is associated with elevated production of sLAIR1, sLAIR2 (antagonist), and limited C1q (agonist) availability. Since reduced LAIR1 transcripts in SMA were associated with increased acquisition of haemozoin (PfHz) by monocytes (P = .028), we explored the relationship between acquisition of intraleukocytic PfHz, LAIR1 expression, and subsequent impacts on leukocyte signalling in cultured PBMCs from malaria-naïve donors stimulated with physiological concentrations of PfHz (10 µg/mL). Phagocytosis of PfHz reduced LAIR1 transcript and protein expression in a time-dependent manner (P < .050), and inhibited LAIR1 signalling through decreased phosphorylation of LAIR1 (P < .0001) and SH2-domain containing phosphatase-1 (SHP-1) (P < .001). This process was associated with NF-κB activation (P < .0001) and enhanced production of IL-6, IL-1ß, and TNF-α (all P < .0001). INTERPRETATION: Collectively, these findings demonstrate that SMA is characterized by reduced LAIR1 transmembrane expression, reduced C1q, and enhanced production of sLAIR1 and sLAIR2, molecular events which can promote enhanced production of cytokines that contribute to the pathogenesis of SMA. These investigations are important for discovering immune checkpoints that could be future targets of immunotherapy to improve disease outcomes.


Assuntos
Anemia/sangue , Malária Falciparum/sangue , Receptores Imunológicos/genética , Anemia/genética , Anemia/parasitologia , Pré-Escolar , Complemento C1q/metabolismo , Feminino , Hemeproteínas/administração & dosagem , Humanos , Lactente , Interleucina-1beta/sangue , Interleucina-6/sangue , Leucócitos Mononucleares/parasitologia , Malária Falciparum/genética , Malária Falciparum/parasitologia , Masculino , Fagocitose , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/genética
19.
Egypt J Immunol ; 26(1): 101-112, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31333000

RESUMO

Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting all organ systems due to alterations of both innate and adaptive immune systems. Given the importance of several factors that may be incriminated in deregulation of immune system in SLE, we aimed to study MTNR1ß gene polymorphisms rs10830963 C/G, serum levels of melatonin and pro-inflammatory cytokines; TNF-α, IL-6, and IL-1ß in SLE patients and the correlation of these parameters to SLE disease activity and damage index at time of study. Subjects were subdivided into 2 groups: group I: 40 SLE patients attending Alexandria main university hospital and outpatient clinic, and group II: 40 control cases of apparently healthy individuals matched for age and sex. For all cases, MTNR1ß gene polymorphism rs10830963 was analyzed by quantitative RT-PCR, serum levels of melatonin, TNF-α, IL-6 and IL-1ß were detected by ELISA. Activity index (SLEDAI) and damage index (SLEDDI) were assessed in SLE patients. MTNR1ß gene polymorphism rs10830963 genotype in SLE patients showed that 50% had GG, 35% CG and 15% CC. The control group had significantly lower ratios, 5% had GG, 15% CG and 80% CC (P < 0.001). Serum melatonin level was decreased in SLE patients (P < 0.001). Serum levels of TNF-α, IL-6, and IL-1ß were increased in SLE patients compared to controls (P < 0.001, P < 0.001, P < 0.001 respectively). There was no correlation between serum melatonin level, TNF-α, IL-6, and IL-1ß with SLEDAI or SLEDDI. In conclusion, MTNR1ß gene polymorphism rs10830963 G allele may contribute in SLE pathogenesis. Inflammatory cytokines; TNF-α, IL-6, IL-1ß may have role in SLE disease manifestations. Targeting immunoregulators as melatonin and proinflammatory cytokines in SLE treatment strategy can be a promising way to SLE cure.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Melatonina/sangue , Polimorfismo Genético , Receptor MT2 de Melatonina/genética , Estudos de Casos e Controles , Egito , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Lúpus Eritematoso Sistêmico/sangue , Fator de Necrose Tumoral alfa/sangue
20.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2637-2643, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359734

RESUMO

To investigate the effect of Fuyanshu Capsules combined with Western medicine antibiotics on symptoms and inflammatory factors IL-10 and IL-1ß in patients with pelvic inflammatory disease and its possible mechanism. Totally 112 patients with pelvic inflammatory disease of damp-heat stagnation treated since April 2017 to April 2018 were randomly divided into treatment group( group A,57 cases) and control group( group B,55 cases). The treatment group was given Fuyanshu Capsules for 56 d,and levofloxacin hydrochloride tablets and metronidazole tablets for 14 d. The control group was given Fuyanshu Capsules as its analogue. The curative rate,effective rate and inefficiency,serum IL-10 and IL-1ß levels were compared between the two groups. The curative effect was evaluated with McCormack score and traditional Chinese medicine( TCM) syndrome score. The recurrence rate and chronic pelvic pain were followed up after one menstrual cycle. It was found that the curative rate and effective rate of group A were higher than those of group B after treatment. After 28 d of treatment,there was a difference in the effective rate of TCM syndrome score between group A and group B( 62. 71% vs 8. 47%,P < 0. 01). After 56 d of treatment,serum IL-10 increased,while IL-1ß decreased in group A,which was significantly different from that in group B( P<0. 01). The recurrence rate of PID and chronic pelvic pain in group A were significantly lower than those in group B( P<0. 01). The results showed that Fuyanshu Capsules combined with levofloxacin and metronidazole could alleviate the clinical symptoms and signs of chronic pelvic inflammation of damp-heat stagnation type,reduce the recurrence rate of pelvic inflammation,relieve pelvic pain,and alleviate the inflammation status of patients by regulating the expression of IL-10 and IL-1ß in peripheral serum.


Assuntos
Antibacterianos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Inflamatória Pélvica/tratamento farmacológico , Cápsulas , Feminino , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Levofloxacino , Medicina Tradicional Chinesa , Metronidazol
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