Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.671
Filtrar
1.
Biochemistry (Mosc) ; 86(6): 693-703, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34225592

RESUMO

Differential effect of the neonatal proinflammatory stress (NPS) on the development of neuroinflammation in the hippocampus and induction of the depressive-like behavior in juvenile and adult male and female rats was studied. NPS induction by bacterial lipopolysaccharide in the neonatal period upregulated expression of the Il6 and Tnf mRNAs accompanied by the development of depressive-like behavior in the adult male rats. NPS increased expression of the mRNAs for fractalkine and its receptor in the ventral hippocampus of the juvenile male rats, but did not affect expression of mRNAs for the proinflammatory cytokines and soluble form of fractalkine. NPS downregulated expression of fractalkine mRNA in the dorsal hippocampus of juvenile males. No significant effects of NPS were found in the female rats. Therefore, the NPS induces long-term changes in the expression of neuroinflammation-associated genes in different regions of the hippocampus, which ultimately leads to the induction of neuroinflammation and development of depressive-like behavior in male rats.


Assuntos
Quimiocina CX3CL1/genética , Depressão/etiologia , Hipocampo/metabolismo , Inflamação/metabolismo , Interleucina-6/genética , Fator de Necrose Tumoral alfa/genética , Animais , Animais Recém-Nascidos , Receptor 1 de Quimiocina CX3C/genética , Depressão/genética , Depressão/metabolismo , Depressão/fisiopatologia , Feminino , Regulação da Expressão Gênica , Hipocampo/patologia , Hipocampo/fisiopatologia , Inflamação/induzido quimicamente , Inflamação/genética , Lipopolissacarídeos/toxicidade , Masculino , Ratos , Caracteres Sexuais
2.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199463

RESUMO

Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn's disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.


Assuntos
Proliferação de Células/genética , Doença de Crohn/terapia , Células Epiteliais/metabolismo , Organoides/crescimento & desenvolvimento , Adulto , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Células Epiteliais/patologia , Feminino , Humanos , Íleo/crescimento & desenvolvimento , Íleo/lesões , Íleo/patologia , Mucosa Intestinal/crescimento & desenvolvimento , Mucosa Intestinal/patologia , Intestinos/diagnóstico por imagem , Intestinos/lesões , Masculino , Pessoa de Meia-Idade , Organoides/metabolismo , Regeneração/genética , Transdução de Sinais/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Fator de Necrose Tumoral alfa/genética , Cicatrização/genética
3.
Mol Med Rep ; 24(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34132373

RESUMO

Coronavirus disease 2019 (COVID­19), caused by the severe acute respiratory syndrome coronavirus­2 (SARS­CoV­2), led to an outbreak of viral pneumonia in December 2019. The present study aimed to investigate the host inflammatory response signature­caused by SARS­CoV­2 in human corneal epithelial cells (HCECs). The expression level of angiotensin­converting enzyme 2 (ACE2) in the human cornea was determined via immunofluorescence. In vitro experiments were performed in HCECs stimulated with the SARS­CoV­2 spike protein. Moreover, the expression levels of ACE2, IL­8, TNF­α, IL­6, gasdermin D (GSDMD) and IL­1ß in HCECs were detected using reverse transcription­quantitative PCR and/or western blotting. It was identified that ACE2 was expressed in normal human corneal epithelium and HCECs cultured in vitro. Furthermore, the expression levels of IL­8, TNF­α and IL­6 in HCECs were decreased following SARS­CoV­2 spike protein stimulation, while the expression levels of GSDMD and IL­1ß were increased. In conclusion, the present results demonstrated that the SARS­CoV­2 spike protein suppressed the host inflammatory response and induced pyroptosis in HCECs. Therefore, blocking the ACE2 receptor in HCECs may reduce the infection rate of COVID­19.


Assuntos
Epitélio Corneano/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Adulto , Idoso , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Células Cultivadas , Córnea/citologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Epitélio Corneano/virologia , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a Fosfato/genética , Proteínas de Ligação a Fosfato/metabolismo , Piroptose , Glicoproteína da Espícula de Coronavírus/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
4.
In Vivo ; 35(4): 2099-2106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182485

RESUMO

BACKGROUND/AIM: S100A4 expression is associated with the pathology of chronic inflammatory diseases. In this study, we investigated the role of S100A4 and four inflammatory mediators (IL-1ß, IκB, IL-10, and TNF-α) in human periapical granulomas (PGs). MATERIALS AND METHODS: S100A4 expression in PGs obtained by apicoectomy was examined by immunohistochemistry. Further, the expression of S100A4 and four inflammatory mediators was compared between PGs and healthy gingival tissues (HGTs) using real-time PCR. RESULTS: In the PGs, S100A4 was found to be expressed in endothelial cells and fibroblasts. Furthermore, real-time PCR revealed that the expression of S100A4 and IL-1ß in PGs was significantly higher than that in HGTs. Although a correlation between the expression of S100A4 and IκB or IL-10 was not detected, a positive correlation between the expression of S100A4 and IL-1ß or TNF-α was observed. CONCLUSION: The expression of S100A4 correlates with the pathogenesis of PGs.


Assuntos
Granuloma Periapical , Células Endoteliais , Gengiva , Humanos , Mediadores da Inflamação , Granuloma Periapical/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Fator de Necrose Tumoral alfa/genética
5.
Ecotoxicol Environ Saf ; 221: 112448, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174739

RESUMO

Atmospheric PM2.5 can induce airway inflammation and mucin secretion. MUC5B is required for airway defense. However, the research on the role of MUC5B in airway inflammation induced by atmospheric PM2.5 remains limited. This study was designed to explore the role of MUC5B in airway inflammation induced by atmospheric PM2.5. In vivo, Wistar rats were exposed to 0, 1.5, 7.5, 37.5 mg/ kg PM2.5 saline suspension via intratracheal instillation. HE staining and AB-PAS staining were used to observe the airway inflammation and goblet cell hyperplasia. In vitro, normal A549 cells and MUC5B-knockdown A549 cells were exposed to 0, 100, 200 and 400 µg/mL PM2.5 for 6 h, 12 h, 24 h and 48 h. ELISA was used to measure the levels of TNF-α and IL-1ß in serum and bronchoalveolar lavage fluid of rats and in cell culture. Real time-PCR and ELISA were used to quantify the mRNA and protein levels of MUC5B in trachea and lung of rats and in A549 cells. PM2.5 could cause the infiltration of inflammatory cells and increase the mucus secretions and goblet cell metaplasia. MUC5B is related to rats' airway inflammation induced by PM2.5. A549 cells exposed to PM2.5 in higher concentration and longer time, the protein level of MUC5B was significantly increased, while the levels of IL-1ß, TNF-α and MUC5B mRNA were significantly decreased. Compared with normal A549 cells, the levels of IL-1ß and TNF-α were significantly higher in Muc5b-knockdown cells. Atmospheric PM2.5 can induce airway inflammation and mucin secretion. MUC5B played a critical role in controlling the inflammatory response induced by PM2.5.


Assuntos
Inflamação/metabolismo , Mucina-5B/metabolismo , Material Particulado/toxicidade , Células A549 , Animais , Líquido da Lavagem Broncoalveolar/química , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Pulmão/metabolismo , Masculino , Mucina-5B/genética , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(5): 630-632, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34112308

RESUMO

Sepsis is a clinical syndrome caused by the host reaction disorder induced by infection, which leads to serious organ function damage. Sepsis is a serious disease with high mortality, which is the main reason of death caused by infection. Single nucleotide polymorphisms (SNP) is one of the most common genetic variants in human, and is closely related to the genetic susceptibility, early diagnosis, disease development and prognosis of sepsis. This article makes a review on the relationship between CD14, Toll like receptor (TLR), tumor necrosis factor (TNF), interleukins (IL-1 and IL-6), plasminogen activator inhibitor 1 (PAI-1), angiotensin converting enzyme (ACE) and other gene polymorphisms and genetic susceptibility of sepsis, in order to affect in sepsis on the early prediction, diagnosis, and treatment.


Assuntos
Predisposição Genética para Doença , Sepse , Humanos , Polimorfismo de Nucleotídeo Único , Sepse/genética , Receptores Toll-Like , Fator de Necrose Tumoral alfa/genética
7.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063554

RESUMO

Acute lung injury (ALI) afflicts approximately 200,000 patients annually and has a 40% mortality rate. The COVID-19 pandemic has massively increased the rate of ALI incidence. The pathogenesis of ALI involves tissue damage from invading microbes and, in severe cases, the overexpression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). This study aimed to develop a therapy to normalize the excess production of inflammatory cytokines and promote tissue repair in the lipopolysaccharide (LPS)-induced ALI. Based on our previous studies, we tested the insulin-like growth factor I (IGF-I) and BTP-2 therapies. IGF-I was selected, because we and others have shown that elevated inflammatory cytokines suppress the expression of growth hormone receptors in the liver, leading to a decrease in the circulating IGF-I. IGF-I is a growth factor that increases vascular protection, enhances tissue repair, and decreases pro-inflammatory cytokines. It is also required to produce anti-inflammatory 1,25-dihydroxyvitamin D. BTP-2, an inhibitor of cytosolic calcium, was used to suppress the LPS-induced increase in cytosolic calcium, which otherwise leads to an increase in proinflammatory cytokines. We showed that LPS increased the expression of the primary inflammatory mediators such as toll like receptor-4 (TLR-4), IL-1ß, interleukin-17 (IL-17), TNF-α, and interferon-γ (IFN-γ), which were normalized by the IGF-I + BTP-2 dual therapy in the lungs, along with improved vascular gene expression markers. The histologic lung injury score was markedly elevated by LPS and reduced to normal by the combination therapy. In conclusion, the LPS-induced increases in inflammatory cytokines, vascular injuries, and lung injuries were all improved by IGF-I + BTP-2 combination therapy.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Anilidas/farmacologia , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Tiadiazóis/farmacologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/virologia , Anilidas/uso terapêutico , Animais , COVID-19/complicações , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/genética , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/uso terapêutico , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tiadiazóis/uso terapêutico , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
8.
Biomolecules ; 11(5)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069869

RESUMO

Several RNA viruses, including SARS-CoV-2, can infect or use the eye as an entry portal to cause ocular or systemic diseases. Povidone-Iodine (PVP-I) is routinely used during ocular surgeries and eye banking as a cost-effective disinfectant due to its broad-spectrum antimicrobial activity, including against viruses. However, whether PVP-I can exert antiviral activities in virus-infected cells remains elusive. In this study, using Zika (ZIKV) and Chikungunya (CHIKV) virus infection of human corneal and retinal pigment epithelial cells, we report antiviral mechanisms of PVP-I. Our data showed that PVP-I, even at the lowest concentration (0.01%), drastically reduced viral replication in corneal and retinal cells without causing cellular toxicity. Antiviral effects of PVP-I against ZIKV and CHIKV were mediated by direct viral inactivation, thus attenuating the ability of the virus to infect host cells. Moreover, one-minute PVP-I exposure of infected ocular cells drastically reduced viral replication and the production of infectious progeny virions. Furthermore, viral-induced (CHIKV) expression of inflammatory genes (TNF-α, IL-6, IL-8, and IL1ß) were markedly reduced in PVP-I treated corneal epithelial cells. Together, our results demonstrate potent antiviral effects of PVP-I against ZIKV and CHIKV infection of ocular cells. Thus, a low dose of PVP-I can be used during tissue harvesting for corneal transplants to prevent potential transmission of RNA viruses via infected cells.


Assuntos
Antivirais/farmacologia , Povidona-Iodo/farmacologia , Vírus de RNA/fisiologia , Replicação Viral/efeitos dos fármacos , Animais , Linhagem Celular , Vírus Chikungunya/fisiologia , Chlorocebus aethiops , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/virologia , SARS-CoV-2/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Células Vero , Zika virus/fisiologia
9.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072918

RESUMO

We previously showed that Lactiplantibacillus plantarum K8 and its cell wall components have immunoregulatory effects. In this study, we demonstrate that pre-treatment of L. plantarum K8 lysates reduced LPS-induced TNF-α production in THP-1 cells by down-regulating the early signals of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The down-regulation of signals may be caused by the induction of negative regulators involved in toll-like receptor (TLR)-mediated signaling. However, co-treatment with high concentrations of L. plantarum K8 lysates and lipopolysaccharide (LPS) activated the late signaling of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB pathways and resulted in the induction of absent in melanoma 2 (AIM2) inflammasome-mediated interleukin (IL)-1ß secretion. Intraperitoneal injection of L. plantarum K8 lysates in LPS-induced endotoxin shock mice alleviated mortality and reduced serum tumor-necrosis factor (TNF)-α, IL-1ß, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. In addition, the mRNA levels of TNF-α, IL-1ß, and IL-6 decreased in livers from mice injected with L. plantarum K8 followed by LPS. Hematoxylin and eosin (H&E) staining of the liver showed that the cell size was enlarged by LPS injection and slightly reduced by L. plantarum K8 lysate pre-injection followed by LPS injection. Macrophage infiltration of the liver also decreased in response to the combination injection compared with mice injected with only LPS. Taken together, our results show that although L. plantarum K8 lysates differentially regulated the production of LPS-induced inflammatory cytokines in THP-1 cells, the lysates inhibited overall inflammation in mice. Thus, this study suggests that L. plantarum K8 lysates could be developed as a substance that modulates immune homeostasis by regulating inflammation.


Assuntos
Inflamação/genética , Lactobacillaceae/química , Fígado/efeitos dos fármacos , Choque Séptico/genética , Animais , Proteínas de Ligação a DNA/genética , Endotoxinas/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-6/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/toxicidade , Fígado/metabolismo , Fígado/patologia , Camundongos , NF-kappa B/genética , Choque Séptico/induzido quimicamente , Choque Séptico/patologia , Fator de Necrose Tumoral alfa/genética
10.
Zhen Ci Yan Jiu ; 46(5): 353-61, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085456

RESUMO

OBJECTIVE: To explore the effect of electroacupuncture (EA) on the ability of spatial learning-memory and the expression of IL-1ß, IL-6 and TNF-α in the hippocampus and spleen tissues and the number of hippocampal neurons and spleen lymphocytes in Alzheimer's disease (AD) mice, so as to study its mechanisms underlying improvement of AD. METHODS: Twenty-four SAMP8 mice were randomly and equally divided into AD model, EA and medication groups, and 8 SAMR1 mice were used as the control group. EA (2 Hz, 0.1 mA) was applied to "Baihui"(GV20) and "Yintang"(EX-HN3) for 20 min in the EA group, and intragastric administration of donepezil hydrochloride (0.92 mg/kg) was applied in the medication group, once daily for 15 d. The learning-memory ability was determined by Morris water maze task, and the histopathological changes of hippocampus were observed after H.E. staining, followed by determining neurons and the number of splenic lymphocytes. The expression levels of IL-1ß, IL-6 and TNF-α in the hippocampus and spleen were detected by immunohistochemistry and Western blot, respectively. RESULTS: After mode-ling, the escape latency of place navigation test in the Morris water maze, the spleen index, immunoactivity and expression levels of IL-1ß, IL-6 and TNF-α proteins in the hippocampus and spleen tissues were significantly increased (P<0.05, P<0.01). Compared with the model group, the escape latency, spleen index, immunoactivity and expression levels of IL-1ß, IL-6 and TNF-α proteins in both hippocampus and spleen were significantly down-regulated in the medication (except the escape latency) and EA groups (P<0.01, P<0.05). The effect of EA was evidently superior to that of medication in shortening the escape latency, lowering the spleen index, and immunoactivity of hippocampal IL-6 and splenic TNF-α immunoactivity (P<0.01, P<0.05). Outcomes of H.E. staining showed disordered arrangement of neurons with nuclear pyknosis or apoptosis in partial neurons in the hippocampus, and thickened and swollen spleen capsule tissue with loose structure and an increased number of lymphocytes in the model group, which was relatively milder in the EA and medication groups. CONCLUSION: EA can improve the learning-memory ability of AD mice, which may be associated with its effect in relieving the inflammation reaction in the hippocampus and spleen tissues.


Assuntos
Doença de Alzheimer , Eletroacupuntura , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Animais , Hipocampo , Interleucina-6/genética , Camundongos , Baço , Fator de Necrose Tumoral alfa/genética
11.
Cancer Med ; 10(10): 3346-3357, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33932127

RESUMO

BACKGROUND: Chronic alcohol consumption is more frequently associated with advanced, aggressive hepatocellular carcinoma (HCC) tumors. Alcohol adversely impacts ER/Golgi membrane trafficking and Golgi protein N-glycosylation in hepatocytes; these effects have been attributed (in part) to dysregulated adenosine diphosphate-ribosylation factor (ARF) GTPase signaling. Here, we investigated the role of the ARF GTPase guanine exchange factor PSD4 in HCC progression. METHODS: R-based bioinformatics analysis was performed on publicly available array data. Modulating gene expression was accomplished via lentiviral vectors. Gene expression was analyzed using quantitative real-time PCR and immunoblotting. PSD4 promoter methylation was assessed using quantitative methylation-specific PCR. Phospho-p65(S276)/DNMT1 binding to the PSD4 promoter was analyzed via chromatin immunoprecipitation. We constructed ethanol/DEN-induced and DEN only-induced transgenic murine models of HCC. RESULTS: We identified PSD4 as a hypermethylated, suppressed gene in alcohol-related HCC tumors; however, PSD4 was not dysregulated in all-cause HCC tumors. Certain HCC cell lines also displayed varying degrees of PSD4 downregulation. PSD4 overexpression or knockdown decreased and increased cell migration and invasiveness, respectively. Mechanistically, PSD4 transcription was repressed by TNF-α-induced phospho-p65(S276)'s recruitment of DNA methyltransferase 1 (DNMT1), resulting in PSD4 promoter methylation. PSD4 inhibited pro-EMT CDC42 activity, resulting in downregulation of E-cadherin and upregulation of N-cadherin and vimentin. Hepatocyte-specific PSD4 overexpression reduced ethanol/DEN-induced HCC tumor progression and EMT marker expression in vivo. CONCLUSIONS: PSD4 is a hypermethylated, suppressed gene in alcohol-related HCC tumors that negatively modulated pro-EMT CDC42 activity. Furthermore, we present a novel phospho-NF-κB p65(S276)/DNMT1-mediated promoter methylation mechanism by which TNF-α/NF-κB signaling represses PSD4 transcription in HCC cells.


Assuntos
Álcoois/efeitos adversos , Carcinoma Hepatocelular/genética , Epigênese Genética/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Neoplasias Hepáticas/genética , NF-kappa B/genética , Transcrição Genética/genética , Fator de Necrose Tumoral alfa/genética , Consumo de Bebidas Alcoólicas/genética , Animais , Caderinas/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferase 1/genética , Metilação de DNA/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Transgênicos , Gravidez , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Fator de Transcrição RelA/genética
12.
Arch Virol ; 166(8): 2141-2149, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34009439

RESUMO

Porcine circovirus type 3 (PCV3) has been widely detected throughout the world since it was first discovered on pig farms in 2015. PCV3 is closely associated with cardiac and multisystem inflammation, respiratory disease, congenital tremors, myocarditis, diarrhea, encephalitis and neurologic disease, and periarteritis. However, there have been few reports on the relationship between PCV3 and inflammatory pathways. The NF-κB signaling pathway plays an important role in the defense against viral infection. Here, we demonstrate that the capsid protein (Cap) of PCV3 plays a key role in the activation of NF-κB signaling in HEK-293T cells. Furthermore, PCV3 Cap promotes the mRNA expression of the pro-inflammatory cytokines IL6 and TNFα. In addition, PCV3 Cap promotes RIG-I and MDA5 mRNA expression in RIG-like receptor (RLR) signaling and MyD88 mRNA expression in Toll-like receptor (TLR) signaling but does not influence TRIF mRNA expression in TLR signaling. These results show that PCV3 Cap activates NF-κB signaling, possibly through the RLR and the TLR signaling pathways. This work illustrates that PCV3 Cap activates NF-κB signaling and thus may provide a basis for the pathogenesis of PCV3 and the innate immunity of the host.


Assuntos
Proteínas do Capsídeo/imunologia , Circovirus/metabolismo , Citocinas/genética , Transdução de Sinais , Circovirus/imunologia , Proteína DEAD-box 58/genética , Células HEK293 , Humanos , Helicase IFIH1 Induzida por Interferon/genética , Interleucina-6/genética , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/genética
13.
Life Sci ; 278: 119624, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34004254

RESUMO

AIMS: Diabetic nephropathy, a major threat to diabetic patients, is considered as the main reason for end-stage renal disease. Fortunately, incretin-based therapy has been aroused as considerable source to attenuate diabetic renal damage. This study aimed to investigate whether superior protective effects on the progression of diabetic kidney are exerted by glucagon-like peptide-1 analog, exenatide, or dipeptidyl peptidase-4 inhibitor, sitagliptin. MATERIALS AND METHODS: Male Wistar rats were fed high-fat diet for 2 weeks followed by injection of low dose streptozotocin to induce type 2 diabetes mellitus. Four weeks after induction of diabetes, diabetic rats were administered vehicle, exenatide (5 µg/kg/day, SC) or sitagliptin (10 mg/kg/day, orally) for 4 weeks. KEY FINDINGS: Different incretin mimetic agents improved renal function as evident by significant decreases in serum creatinine and urea levels with decline in urinary microalbuminuria and marked improvement in histological alterations. Both treated diabetic rats also exhibited a significant improvement in metabolic intolerance with more pronounced effect of exenatide on glucose regulation. Ameliorated renal oxidative stress alongside significant downregulation in transforming growth factor-beta, tumor necrosis factor-alpha and cleaved-caspase-3 protein expressions in renal tissues were recorded in treated diabetic rats. SIGNIFICANCE: Administration of either exenatide or sitagliptin showed ameliorative effects on early diabetic nephropathy without notable differences between their renal protective effects. However, further clinical studies are still required to ensure their comparative promising effects on the management of renal complication of diabetes.


Assuntos
Caspase 3/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Incretinas/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Caspase 3/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Regulação da Expressão Gênica , Masculino , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/genética
14.
Nat Commun ; 12(1): 2992, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016976

RESUMO

Rapid death of infected cells is an important antiviral strategy. However, fast decisions that are based on limited evidence can be erroneous and cause unnecessary cell death and subsequent tissue damage. How cells optimize their death decision making strategy to maximize both speed and accuracy is unclear. Here, we show that exposure to TNF, which is secreted by macrophages during viral infection, causes cells to change their decision strategy from "slow and accurate" to "fast and error-prone". Mathematical modeling combined with experiments in cell culture and whole organ culture show that the regulation of the cell death decision strategy is critical to prevent HSV-1 spread. These findings demonstrate that immune regulation of cellular cognitive processes dynamically changes a tissues' tolerance for self-damage, which is required to protect against viral spread.


Assuntos
Apoptose/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Macrófagos/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Córnea/imunologia , Córnea/virologia , Modelos Animais de Doenças , Feminino , Herpes Simples/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Microscopia Intravital , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Modelos Imunológicos , Células NIH 3T3 , Técnicas de Cultura de Órgãos , Cultura Primária de Células , Imagem com Lapso de Tempo , Fator de Necrose Tumoral alfa/genética
15.
Wei Sheng Yan Jiu ; 50(2): 261-273, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33985634

RESUMO

OBJECTIVE: To investigate the associations between the polymorphisms and interaction of the interleukin 6(IL-6) genes at-634 C/G, -174 G/C, -1363 G/T loci, as well as the interactions between the three loci and tumor necrosis factor(TNF-α), and peripheral blood leukocytes(white blood cell, WBC) with metabolic syndrome(MS). METHODS: Using the case-control research method, according to the inclusion and exclusion criteria, from March 2015 to March 2016 from the General Hospital of Ningxia Medical University and Wuzhong City People's Hospital, 376 unrelated cases and 408 control groups were selected. We conducted questionnaire surveys(including general conditions, disease and medication history, family history, etc. ), physical examinations(including height, weight and calculation of body mass index(BMI), waist circumference, hip circumference and calculation of waist-to-hip ratio(WHR), SBP, DBP, etc. ), blood collection and testing(including WBC count, serum TNF-α level and biochemical indicators TG, TC, HDL-C, LDL-C, FPG, UA, AST, ALT, etc. ), and the polymorphism detection of IL-6 gene at-634 C/G, -174 G/C, -1363 G/T sites. The SNPstats online software was used to analyze the relationship between the polymorphisms of IL-6 gene and MS. The SHEsis online software was used to analyze the linkage disequilibrium(LD) of the IL-6 three-site and the relationship between haplotype and MS. GMDR 0. 7 software was used to analyze the interactions among the three sites of IL-6 gene, and one between the three sites and TNF-α and WBC, respectively. RESULTS: Before and after adjustment of sex, age and nationality, the polymorphism at the 3 position of IL-6 gene was not related to the onset of MS in different genetic models(both P> 0. 05). There was a linkage disequilibrium between the three loci of IL-6 gene, but the haploids formed by these three loci were not associated with MS susceptibility(all P> 0. 05). There was no interaction among the three sites, but the two-factor, three-factor, and four-factor interaction models consisting of the three sites and TNF-α were all statistically significant(all P<0. 001) and the replacement tests were all P<0. 001, and were all associated with MS occurrence. The two-factor, three-factor, and four-factor interaction models consisting of the three sites and WBC were all P<0. 01, and the replacement tests were all P<0. 05. The differences were statistically significant, which was related to the onset of MS. CONCLUSION: The IL-6 gene-634 C/G, -174 G/C, and-1363 G/T loci polymorphism may not be significantly associated with the prevalence of MS. Interactions between the three sites and TNF-α and WBC levels can significantly increase the risk of MS.


Assuntos
Síndrome Metabólica , Humanos , Interleucina-6/genética , Leucócitos , Síndrome Metabólica/genética , Fator de Necrose Tumoral alfa/genética , Circunferência da Cintura
16.
Gene ; 790: 145690, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-33961973

RESUMO

OBJECTIVE: During extracorporeal circulation, blood is in contact with nonendothelial surfaces. The increase in the amount of blood touching the non-endothelial surface increases the damage to the blood elements. This initiates and increases oxidative stress. Increased oxidative stress leads to the activation of antioxidant systems. These two systems work gradually in the process of Cardiopulmonary Bypass. This study aims to investigate the changes of TNF-α, Nrf2 and HO-1 gene expression in extracorporeal circulation. MATERIALS AND METHODS: Fifteen patients who underwent open heart surgery were included in the study. Blood samples were taken preoperatively, during cardiopulmonary bypass (CPB) and 24 hours postoperatively. TNF-α, Nrf2 and HO-1 gene expressions in plasma samples were studied by using appropriate kits. Changes in gene expressions were compared. RESULTS: TNF-α gene expression increased during CPB compared to preoperative levels (p <0.05). Similarly, Nrf-2 gene expression increased significantly during CPB (p <0.001) and decreased postoperatively (p <0.001). There was a significant increase in HO-1 gene expression during CPB (p <0.01). Postoperatively, this increase was found to decrease similar to Nrf2 (p <0.05). CONCLUSIONS: According to the results, TNF-α, Nrf2, HO-1 gene expressions increase during CPB and these values decrease after the operation. This shows that oxidative stress and inflammatory processes start with CPB and antioxidant processes start similarly. With the termination of CPB, both processes are terminated. This has been demonstrated by gene expressions. Future studies will make it easier to understand these processes.


Assuntos
Ponte Cardiopulmonar/métodos , Doenças Cardiovasculares/metabolismo , Regulação da Expressão Gênica , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/cirurgia , Feminino , Heme Oxigenase-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Estudos Prospectivos , Fator de Necrose Tumoral alfa/genética
17.
Biomed Res Int ; 2021: 5595368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954182

RESUMO

Despite the beneficial effects of exercise and physical activity, there is little knowledge about the effects of different types of physical activity on neural function. The present study assessed the effects of two types of selected aerobic exercises prior to stroke induction and characterized the expression of TrkB, TNF-α, and MMP2 genes in vivo. Forty male adult Wistar rats were exposed to aerobic exercises following randomization into four groups, including swimming + MCAO (Middle Cerebral Artery Occlusion) (n = 10), treadmill training + MCAO (n = 10), MCAO (n = 10), and control (n = 10). The swimming + MCAO group included swimming for 30 minutes each day, while the treadmill training + MCAO group program involved running for 30 minutes each day at an intensity of 15 m/min, for three weeks, five days a week. Neurological deficit was assessed using modified criteria at 24 h after the onset of cerebral ischemia. In the control group, the animals worked freely for three weeks without undergoing ischemia. The MCAO group also operated freely for three weeks after they underwent a stroke. Both training groups underwent ischemia after three weeks of training. TrkB, TNF-α, and MMP2 gene expressions were increased in the MCAO+ swimming training and in the MCAO + running training group compared to the control and MCAO groups, respectively. Preconditioning aerobic exercises significantly increased brain trophic support and reduced brain damage conditions in exercise groups, which support the importance of aerobic exercise in the prevention and treatment of stroke.


Assuntos
Metaloproteinase 2 da Matriz/metabolismo , Condicionamento Físico Animal/fisiologia , Receptor trkB/metabolismo , Acidente Vascular Cerebral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/genética , Ratos , Ratos Wistar , Receptor trkB/análise , Receptor trkB/genética , Natação/fisiologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética
18.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1667-1673, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982466

RESUMO

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.


Assuntos
Dendrobium , Lipopolissacarídeos , Animais , Mucosa Intestinal , Masculino , Camundongos , NF-kappa B , Pós , Fator de Necrose Tumoral alfa/genética
19.
Zhongguo Gu Shang ; 34(4): 363-7, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33896138

RESUMO

OBJECTIVE: To investigate the expression and clinical significance of receptor interacting protein serine-threonine kinases 1 (RIPK1) in the nucleus pulposus of patients with lumbar disc herniation (LDH). METHODS: Nucleus pulposus tissue specimens of 40 patients with LDH patients underwent surgical treatment from January 2016 to January 2018 as the case group, and nucleus pulposus tissue specimens of 30 patients with lumbar spine fracture underwent surgical treatment at the same time as the control group. The expression of RIPK1 mRNA and protein of receptor interaction were detected by polymerase chain reaction (PCR) and Western blot, respectively. The expression of RIPK1 protein in the nucleus pulposus were detected by immunohistochemical staining. The concentrations of RIPK1 and tumor necrosis factor-α (TNF-α) in nucleus pulposus were detected by ELISA method. The relationship between the concentrations of RIPK1, TNF-α in nucleus pulposus and the Pearce grade of LDH patients was analyzed by one-way ANOVA. The correlation between RIPK1 and TNF-α was analyzed by Pearson. RESULTS: RIPK1 was weakly positively expressed in nucleus pulposus of control group, and RIPK1 protein was positively or strongly positively expressed in case group. The expression of RIPK1 mRNA in nucleus pulposus of case group was higher than that of control group (P<0.05). The expression of RIPK1 protein in nucleus pulposus of case group was higher than that of control group(P<0.05). The RIPK1 concentration in nucleus pulposus of case group was higher than that of control group (P=0.012). The concentration of TNF-α in nucleus pulposus of case group was significantly higher than that of control group (P=0.009). There were significantdifferences in concentrations of RIPK1 and TNF-α in nucleus pulposus of LDH patients with different Pearce classification (P>0.05). The concentration of RIPK1 and TNF-α in nucleus pulposus increased significantly with the increase of Pearce grade. Pearson correlation analysis showed that there was a significant positive correlation between RIPK1 and TNF-α in nucleus pulposus of LDH patients (r=0.781, P<0.001). CONCLUSION: The expression levels of RIPK1 mRNA and protein in the intervertebral disc tissues of LDH patients are higher than those of normal intervertebral disc tissues, and increased with the increase of Pearce grade, which may be an important factor involved in LDH inflammatory disease.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Disco Intervertebral/metabolismo , Deslocamento do Disco Intervertebral/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
20.
J Biol Chem ; 296: 100630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33823154

RESUMO

Unchecked inflammation can result in severe diseases with high mortality, such as macrophage activation syndrome (MAS). MAS and associated cytokine storms have been observed in COVID-19 patients exhibiting systemic hyperinflammation. Interleukin-18 (IL-18), a proinflammatory cytokine belonging to the IL-1 family, is elevated in both MAS and COVID-19 patients, and its level is known to correlate with the severity of COVID-19 symptoms. IL-18 binds its specific receptor IL-1 receptor 5 (IL-1R5, also known as IL-18 receptor alpha chain), leading to the recruitment of the coreceptor, IL-1 receptor 7 (IL-1R7, also known as IL-18 receptor beta chain). This heterotrimeric complex then initiates downstream signaling, resulting in systemic and local inflammation. Here, we developed a novel humanized monoclonal anti-IL-1R7 antibody to specifically block the activity of IL-18 and its inflammatory signaling. We characterized the function of this antibody in human cell lines, in freshly obtained peripheral blood mononuclear cells (PBMCs) and in human whole blood cultures. We found that the anti-IL-1R7 antibody significantly suppressed IL-18-mediated NFκB activation, reduced IL-18-stimulated IFNγ and IL-6 production in human cell lines, and reduced IL-18-induced IFNγ, IL-6, and TNFα production in PBMCs. Moreover, the anti-IL-1R7 antibody significantly inhibited LPS- and Candida albicans-induced IFNγ production in PBMCs, as well as LPS-induced IFNγ production in whole blood cultures. Our data suggest that blocking IL-1R7 could represent a potential therapeutic strategy to specifically modulate IL-18 signaling and may warrant further investigation into its clinical potential for treating IL-18-mediated diseases, including MAS and COVID-19.


Assuntos
Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Fatores Imunológicos/farmacologia , Interleucina-18/genética , Receptores de Interleucina-18/genética , Anti-Inflamatórios/metabolismo , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/biossíntese , COVID-19/tratamento farmacológico , Candida albicans/crescimento & desenvolvimento , Candida albicans/patogenicidade , Regulação da Expressão Gênica , Células HEK293 , Humanos , Fatores Imunológicos/biossíntese , Inflamação , Interferon gama/genética , Interferon gama/imunologia , Interleucina-18/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Síndrome de Ativação Macrofágica/tratamento farmacológico , NF-kappa B/genética , NF-kappa B/imunologia , Cultura Primária de Células , Receptores de Interleucina-18/antagonistas & inibidores , Receptores de Interleucina-18/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...