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1.
Environ Manage ; 64(6): 772-782, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31748948

RESUMO

During the last decade, China's agro-food production has increased rapidly and been accompanied by the challenge of increasing greenhouse gas (GHG) emissions and other environmental pollutants from fertilizers, pesticides, and intensive energy use. Understanding the energy use and environmental impacts of crop production will help identify environmentally damaging hotspots of agro-production, allowing environmental impacts to be assessed and crop management strategies optimized. Conventional farming has been widely employed in wolfberry (Lycium barbarum) cultivation in China, which is an important cash tree crop not only for the rural economy but also from an ecological standpoint. Energy use and global warming potential (GWP) were investigated in a wolfberry production system in the Yellow River irrigated Jingtai region of Gansu. In total, 52 household farms were randomly selected to conduct the investigation using questionnaires. Total energy input and output were 321,800.73 and 166,888.80 MJ ha-1, respectively, in the production system. The highest share of energy inputs was found to be electricity consumption for lifting irrigation water, accounting for 68.52%, followed by chemical fertilizer application (11.37%). Energy use efficiency was 0.52 when considering both fruit and pruned wood. Nonrenewable energy use (88.52%) was far larger than the renewable energy input. The share of GWP of different inputs were 64.52% electricity, 27.72% nitrogen (N) fertilizer, 5.07% phosphate, 2.32% diesel, and 0.37% potassium, respectively. The highest share was related to electricity consumption for irrigation, followed by N fertilizer use. Total GWP in the wolfberry planting system was 26,018.64 kg CO2 eq ha-1 and the share of CO2, N2O, and CH4 were 99.47%, 0.48%, and negligible respectively with CO2 being dominant. Pathways for reducing energy use and GHG emission mitigation include: conversion to low carbon farming to establish a sustainable and cleaner production system with options of raising water use efficiency by adopting a seasonal gradient water pricing system and advanced irrigation techniques; reducing synthetic fertilizer use; and policy support: smallholder farmland transfer (concentration) for scale production, credit (small- and low-interest credit) and tax breaks.


Assuntos
Aquecimento Global , Lycium , Agricultura , Carbono , China , Fertilizantes , Efeito Estufa , Metano , Óxido Nitroso
2.
Front Psychol ; 10: 1959, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31551859

RESUMO

Background: It is well established that increased internet use is related to an increased risk of musculoskeletal pain among adolescents. The relationship between internet addiction (IA), a unique condition involving severe internet overuse, and musculoskeletal pain has, however, not been reported. This study aimed to investigate the association between IA and the risk of musculoskeletal pain among Chinese college students. Methods: A cross-sectional study was conducted among 4211 Chinese college freshmen. IA status was evaluated using the 20-item Young's Internet Addiction Test (IAT). IA was defined as internet addiction score ≥50 points. Musculoskeletal pain was assessed using a self-reported questionnaire. Multiple logistic regression analysis was performed to determine association between IA categories (normal, mild, and moderate-to-severe) and musculoskeletal pain. Results: Among all participants; neck, shoulder, elbow, wrist/hand, and low back and waist pain was reported by 29.2, 33.9, 3.8, 7.9, and 27.9%, respectively. The prevalence of IA was 17.4%. After adjusting for potential confounders, the results showed significant differences in the risk of musculoskeletal pain among different IA categories. The odds ratios (ORs) and 95% confidence intervals (CI) for neck pain with IA categories were 1.000 (reference), 1.451 (1.221, 1.725), and 1.994 (1.608, 2.473), respectively (P for trends: < 0.001). For shoulder pain, these were 1.000 (reference), 1.520 (1.287, 1.795), and 2.057 (1.664, 2.542), respectively (P for trends: < 0.001). For elbow pain, ORs (95% CIs) were 1.000 (reference), 1.627 (1.016, 2.605), and 2.341 (1.382, 3.968), respectively (P for trends: 0.001). Those for wrist/hand pain were 1.000 (reference), 1.508 (1.104, 2.060), and 2.236 (1.561, 3.202), respectively (P for trends: < 0.001). For low back and waist pain with severe IA categories, these were 1.000 (reference), 1.635 (1.368, 1.955), and 2.261 (1.813, 2.819), respectively (P for trends: < 0.001). Conclusion: This cross-sectional study showed that severe IA was associated with a higher risk of musculoskeletal pain in Chinese college freshmen. In future research, it will be necessary to explore causality regarding this relationship using interventional studies.

3.
Am J Physiol Cell Physiol ; 317(2): C262-C269, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116584

RESUMO

Phenotypic transformation of vascular smooth muscle cells is a key phenomenon in the development of aortic dissection disease. However, the molecular mechanisms underlying this phenomenon have not been fully understood. We used ß-BAPN combined with ANG II treatment to establish a disease model of acute aortic dissection (AAD) in mice. We first examined the gene expression profile of aortic tissue in mice with AAD using a gene chip, followed by confirmation of DExH-box helicase 9 (DHX9) expression using RT-PCR, Western blot, and immunofluorescence analysis. We further developed vascular smooth muscle cell-specific DHX9 conditional knockout mice and conducted differential and functional analysis of gene expression and alternative splicing in mouse vascular smooth muscle cells. Finally, we examined the involvement of DHX9 in Krüppel-like factor 5 (KLF5) mRNA alternative splicing. Our study reported a significant decrease in the expression of DHX9 in the vascular smooth muscle cells (VSMCs) of mice with AAD. The smooth muscle cell-specific knockout of DHX9 exacerbated the development of AAD and altered the transcriptional level expression of many smooth muscle cell phenotype-related genes. Finally, we reported that DHX9 may induce alternative splicing of KLF5 mRNA by bridging YB-1. These results together suggested a new pathogenic mechanism underlying the development of AAD, and future research of this mechanism may help identify effective therapeutic intervention for AAD.

4.
Cell Res ; 29(1): 42-53, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30514903

RESUMO

The cross-talk between cellular lipid metabolism and the innate immune responses remains obscure. In addition to presenting lipid antigens to Natural Killer T-cells (NKT cells), the Cluster of Differentiation 1D Glycoprotein (CD1d) might mediate reverse signaling in antigen-presenting cells (APCs). Here we found CD1d deficiency attenuated Toll-like receptor (TLR)-triggered inflammatory innate responses in macrophages and dendritic cells, protecting mice from endotoxin shock. TLR activation in macrophages induced metabolic changes of glycosphingolipids (GSLs), among which glycolipid isoglobotrihexosylceramide (iGb3) was rapidly produced. The endogenously generated iGb3 bound CD1d in endosomal compartments and then synergized with the initially activated TLR signal to induce Tyr332 phosphorylation of CD1d intracellular domain. This led to the recruitment and activation of proline-rich tyrosine kinase 2 (Pyk2). Pyk2 interacted with IκB kinase ß (IKKß) and TANK-binding kinase 1 (TBK1), and enhanced tyrosine phosphorylation of Tyr188/199 of IKKß and Tyr179 of TBK1 and thus, their activation to promote full activation of TLR signaling. Thus, intracellular CD1d reverse signaling, triggered by endogenous iGb3, amplifies inflammatory innate responses in APCs. Our findings identify a non-canonical function of CD1d reverse signaling activated by lipid metabolite in the innate immune response.

5.
Mol Pain ; : 1744806918808150, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30280656

RESUMO

Neuroinflammation plays an important role in the induction and maintenance of chronic pain. Orchestra of pattern-recognition receptors (PRRs) induced pro-inflammatory and anti-inflammatory cytokines are critical for inflammation homeostasis. CD11b on macrophages could inhibit toll like receptor (TLR) activation induced inflammatory responses. However, the function of CD11b on microglia remains unknown. In the current study, we demonstrated that CD11b deficient microglia cells produced more inflammatory cytokines such as IL-6 and TNF-α, while less anti-inflammatory cytokines. Signal transduction assay confirmed that NF-κB activation was increased in CD11b deficient microglia cells, which was resulted from decreased activation of Src. Inhibition of Src by PP1 increased inflammation in wildtype microglia cells significantly, but not in CD11b deficient microglia cells. In vivo, CD11b deficient mice were more susceptible to CCI induced allodynia and hyperalgesia with significantly more inflammatory cytokines expression. All these results indicated that the regulatory function of CD11b-Src signal pathway on both inflammatory and anti-inflammatory cytokines in microglia cells, which is a potential target in neuropathic pain treatment.

6.
Math Biosci Eng ; 14(5-6): 1279-1299, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29161861

RESUMO

Schistosomiasis, a parasitic disease caused by \textit{ Schistosoma Japonicum}, is still one of the most serious parasitic diseases in China and remains endemic in seven provinces, including Hubei, Anhui, Hunan, Jiangsu, Jiangxi, Sichuan, and Yunnan. The monthly data of human schistosomiasis cases in Hubei, Hunan, and Anhui provinces (lake and marshland regions) released by the Chinese Center for Disease Control and Prevention (China CDC) display a periodic pattern with more cases in late summer and early autumn. Based on this observation, we construct a deterministic model with periodic transmission rates to study the seasonal transmission dynamics of schistosomiasis in these lake and marshland regions in China. We calculate the basic reproduction number R0, discuss the dynamical behavior of solutions to the model, and use the model to fit the monthly data of human schistosomiasis cases in Hubei. We also perform some sensitivity analysis of the basic reproduction number R0 in terms of model parameters. Our results indicate that treatment of at-risk population groups, improving sanitation, hygiene education, and snail control are effective measures in controlling human schistosomiasis in these lakes and marshland regions.


Assuntos
Lagos , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/transmissão , Estações do Ano , Áreas Alagadas , Algoritmos , Animais , Número Básico de Reprodução , China/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Infectologia/métodos , Modelos Teóricos , Schistosoma japonicum , Caramujos/parasitologia
7.
Sci Rep ; 7: 40035, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-28059131

RESUMO

Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation.


Assuntos
Diosgenina/análogos & derivados , Encefalite/tratamento farmacológico , Endotoxemia/complicações , Neurogênese/efeitos dos fármacos , Agonistas do Receptor de Serotonina/metabolismo , Serotonina/metabolismo , Animais , Diosgenina/metabolismo , Perfilação da Expressão Gênica , Proteína Glial Fibrilar Ácida/análise , Hipocampo/patologia , Hipocampo/fisiologia , Antígeno Ki-67/análise , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/análise , Neuropeptídeos/análise , Reação em Cadeia da Polimerase em Tempo Real
8.
Comput Math Methods Med ; 2015: 582625, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26246849

RESUMO

In order to investigate the transmission mechanism of the infectious individual with Ebola virus, we establish an SEIT (susceptible, exposed in the latent period, infectious, and treated/recovery) epidemic model. The basic reproduction number is defined. The mathematical analysis on the existence and stability of the disease-free equilibrium and endemic equilibrium is given. As the applications of the model, we use the recognized infectious and death cases in Guinea to estimate parameters of the model by the least square method. With suitable parameter values, we obtain the estimated value of the basic reproduction number and analyze the sensitivity and uncertainty property by partial rank correlation coefficients.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/transmissão , Algoritmos , Número Básico de Reprodução , Coeficiente de Natalidade , Controle de Doenças Transmissíveis , Doenças Transmissíveis/epidemiologia , Surtos de Doenças , Epidemias , Guiné , Humanos , Análise dos Mínimos Quadrados , Matemática , Modelos Teóricos
9.
J Environ Manage ; 157: 303-10, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25925391

RESUMO

The largest global source of anthropogenic CO2 emissions comes from the burning of fossil fuel and approximately 30% of total net emissions come from land use and land use change. Forestation and reforestation are regarded worldwide as effective options of sequestering carbon to mitigate climate change with relatively low costs compared with industrial greenhouse gas (GHG) emission reduction efforts. Cash trees with a steady augmentation in size are recognized as a multiple-beneficial solution to climate change in China. The reporting of C changes and GHG emissions for sustainable land management (SLM) practices such as afforestation is required for a variety of reasons, such as devising land management options and making policy. The Carbon Benefit Project (CBP) Simple Assessment Tool was employed to estimate changes in soil organic carbon (SOC) stocks and GHG emissions for wolfberry (Lycium barbarum L.) planting on secondary salinized land over a 10 year period (2004-2014) in the Jingtai oasis in Gansu with salinized barren land as baseline scenario. Results show that wolfberry plantation, an intensively managed ecosystem, served as a carbon sink with a large potential for climate change mitigation, a restorative practice for saline land and income stream generator for farmers in soil salinized regions in Gansu province. However, an increase in wolfberry production, driven by economic demands, would bring environmental pressures associated with the use of N fertilizer and irrigation. With an understanding of all of the components of an ecosystem and their interconnections using the Drivers-Pressures-State-Impact-Response (DPSIR) framework there comes a need for strategies to respond to them such as capacity building, judicious irrigation and institutional strengthening. Cost benefit analysis (CBA) suggests that wolfberry cultivation was economically profitable and socially beneficial and thus well-accepted locally in the context of carbon sequestration. This study has important implications for Gansu as it helps to understand the role cash trees can play in carbon emission reductions. Such information is necessary in devising management options for sustainable land management (SLM).


Assuntos
Carbono/química , Lycium , Poluentes do Solo/química , Solo/química , Sequestro de Carbono , China , Conservação dos Recursos Naturais/economia , Análise Custo-Benefício , Humanos , Modelos Teóricos
10.
Biochem Biophys Res Commun ; 456(1): 225-31, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-25446127

RESUMO

Fibroblast growth factors (FGFs) are a family of structurally related heparin-binding proteins with diverse biological functions. FGFs participate in mitogenesis, angiogenesis, cell proliferation, development, differentiation and cell migration. Here, we investigated the potential effect of FGF10, a member of FGFs, on neuron survival in oxygen-glucose deprivation (OGD) model. In primary cultured mouse cortical neurons upon OGD, FGF10 treatment (100 and 1000 ng/ml) attenuated the decrease of cell viability and rescued the LDH release. Tuj-1 immunocytochemistry assay showed that FGF10 promoted neuronal survival. Apoptosis assay with Annexin V+PI by flow cytometry demonstrated that FGF10 treatment reduced apoptotic cell proportion. Moreover, immunoblotting showed that FGF10 alleviated the cleaved caspase-3 upregulation caused by OGD. FGF10 treatment also depressed the OGD-induced increase of caspase-3, -8 and -9 activities. At last, we found FGF10 triggered heme oxygenase-1 (HO-1) protein expression rather than hypoxia-inducible factor-1 (HIF-1), AMP-activated protein kinase (AMPK) signaling and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Knockdown of HO-1 by siRNA partly abolished the neuroprotection of FGF10 in OGD model. In summary, our observations provide the first evidence for the neuroprotective function of FGF10 against ischemic neuronal injury and suggest that FGF10 may be a promising agent for treatment of ischemic stroke.


Assuntos
Glicemia/metabolismo , Fator 10 de Crescimento de Fibroblastos/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , Animais , Apoptose , Isquemia Encefálica/patologia , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Córtex Cerebral/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células PC12 , RNA Interferente Pequeno/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Acidente Vascular Cerebral/patologia
11.
Proc Natl Acad Sci U S A ; 110(27): 11097-102, 2013 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-23776228

RESUMO

Toll-like receptor (TLR) signaling is critical in innate response against invading pathogens. However, the molecular mechanisms for full activation of TLR-triggered innate immunity need to be fully elucidated. The broad complex tramtrack bric-a-brac/poxvirus and zinc finger (BTB/POZ) family is a class of transcription factors involved in many biological processes. However, few BTB/POZ proteins were reported to function in innate immune response. Zinc finger and BTB domain-containing 20 (ZBTB20), a member of BTB/POZ family, functions in neurogenesis and represses α-fetoprotein gene transcription in liver. However, the immunological functions of ZBTB20 remain unknown. Here, we found that myeloid cell-specific ZBTB20 KO mice were resistant to endotoxin shock and Escherichia coli-caused sepsis. ZBTB20 deficiency attenuated TLR-triggered production of proinflammatory cytokines and type I IFN in macrophages, which attributed to higher abundance of IκBα protein and impaired activity of NF-κB. Furthermore, ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription.


Assuntos
Proteínas I-kappa B/antagonistas & inibidores , Proteínas I-kappa B/genética , Supressão Genética , Receptores Toll-Like/fisiologia , Fatores de Transcrição/fisiologia , Transcrição Genética/imunologia , Animais , Regulação para Baixo/genética , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/patologia , Feminino , Proteínas I-kappa B/metabolismo , Imunidade Inata/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/imunologia , Células Mieloides/patologia , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica/genética , Choque Séptico/genética , Choque Séptico/imunologia , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
12.
J Biol Chem ; 288(23): 16225-34, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23609450

RESUMO

Sepsis-associated immunosuppression (SAIS) is regarded as one of main causes for the death of septic patients at the late stage because of the decreased innate immunity with a more opportunistic infection. LPS-tolerized macrophages, which are re-challenged by LPS after prior exposure to LPS, are regarded as the common model of hypo-responsiveness for SAIS. However, the molecular mechanisms of endotoxin tolerance and SAIS remain to be fully elucidated. In addition, negative regulation of the Toll-like receptor (TLR)-triggered innate inflammatory response needs further investigation. Here we show that expression of immune responsive gene 1 (IRG1) was highly up-regulated in the peripheral blood mononuclear cells of septic patients and in LPS-tolerized mouse macrophages. IRG1 significantly suppressed TLR-triggered production of proinflammatory cytokines TNF-α, IL-6, and IFN-ß in LPS-tolerized macrophages, with the elevated expression of reactive oxygen species (ROS) and A20. Moreover, ROS enhanced A20 expression by increasing the H3K4me3 modification of histone on the A20 promoter domain, and supplement of the ROS abrogated the IRG1 knockdown function in breaking endotoxin tolerance by increasing A20 expression. Our results demonstrate that inducible IRG1 promotes endotoxin tolerance by increasing A20 expression through ROS, indicating a new molecular mechanism regulating hypoinflammation of sepsis and endotoxin tolerance.


Assuntos
Proteínas de Ligação a DNA/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hidroliases/imunologia , Tolerância Imunológica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Proteínas Nucleares/imunologia , Proteínas/imunologia , Espécies Reativas de Oxigênio/imunologia , Sepse/imunologia , Ubiquitina-Proteína Ligases/imunologia , Animais , Carboxiliases , Cisteína Endopeptidases , Proteínas de Ligação a DNA/genética , Feminino , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Técnicas de Silenciamento de Genes , Histonas/genética , Histonas/imunologia , Humanos , Hidroliases/genética , Interferon beta/genética , Interferon beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipopolissacarídeos/imunologia , Macrófagos/patologia , Masculino , Camundongos , Monócitos/imunologia , Monócitos/patologia , Proteínas Nucleares/genética , Proteínas/genética , Sepse/genética , Sepse/patologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Ubiquitina-Proteína Ligases/genética
13.
J Immunol ; 190(4): 1685-94, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23296707

RESUMO

TLRs are essential for sensing the invading pathogens and initiating protective immune responses. However, aberrant activation of TLR-triggered inflammatory innate responses leads to the inflammatory disorders and autoimmune diseases. The molecular mechanisms that fine-tune TLR responses remain to be fully elucidated. Protein tyrosine phosphatase with proline-glutamine-serine-threonine-rich motifs (PTP-PEST) has been shown to be important in cell adhesion, migration, and also T cell and B cell activation. However, the roles of PTP-PEST in TLR-triggered immune response remain unclear. In this study, we report that PTP-PEST expression was upregulated in macrophages by TLR ligands. PTP-PEST inhibited TNF-α, IL-6, and IFN-ß production in macrophages triggered by TLR3, TLR4, and TLR9. Overexpression of catalytically inactive mutants of PTP-PEST abolished the inhibitory effects, indicating that PTP-PEST inhibits TLR response in a phosphatase-dependent manner. Accordingly, PTP-PEST knockdown increased TLR3, -4, and -9-triggered proinflammatory cytokine and type I IFN production. PTP-PEST selectively inhibited TLR-induced NF-κB activation, whereas it had no substantial effect on MAPK and IFN regulatory factor 3 activation. Moreover, PTP-PEST directly interacted with IκB kinase ß (IKKß) then inhibited IKKß phosphorylation at Ser(177/181) and Tyr(188/199), and subsequently suppressed IKKß activation and kinase activity as well as downstream NF-κB activation, resulting in suppression of the TLR-triggered innate immune response. Thus, PTP-PEST functions as a feedback-negative regulator of TLR-triggered innate immune responses by selectively impairing IKKß/NF-κB activation.


Assuntos
Regulação para Baixo/imunologia , Quinase I-kappa B/antagonistas & inibidores , Imunidade Inata , NF-kappa B/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 12/química , Proteína Tirosina Fosfatase não Receptora Tipo 12/fisiologia , Receptores Toll-Like/fisiologia , Motivos de Aminoácidos/genética , Motivos de Aminoácidos/imunologia , Animais , Linhagem Celular , Células Cultivadas , Regulação para Baixo/genética , Glutamina/metabolismo , Células HEK293 , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Imunidade Inata/genética , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Prolina/metabolismo , Mapeamento de Interação de Proteínas/métodos , Proteína Tirosina Fosfatase não Receptora Tipo 12/biossíntese , Serina/metabolismo , Treonina/metabolismo , Distribuição Tecidual/genética , Distribuição Tecidual/imunologia , Receptores Toll-Like/antagonistas & inibidores , Receptores Toll-Like/genética
14.
J Zhejiang Univ Sci B ; 14(1): 1-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23303626

RESUMO

Innate immunity is considered to provide the initial defense against infections by viruses, bacteria, fungi, and protozoa. Detection of the signature molecules of invading pathogens by front-line defense cells via various germline-encoded pattern recognition receptors (PRRs) is needed to activate intracellular signaling cascades that lead to transcriptional expression of inflammatory mediators to coordinate the elimination of pathogens and infected cells. To maintain a fine balance between protective immunity and inflammatory pathology upon infection, the innate signaling pathways in the host need to be tightly regulated. MicroRNAs (miRNAs), a new class of small non-coding RNAs, have been recently shown to be potent modulators that function at post-transcriptional levels. Accumulating evidence demonstrates that the involvement of microorganism-encoded and host miRNAs might play instructive roles in the immune response upon infection. Here, we discuss the current knowledge of miRNAs in the regulation of immune response against infections.


Assuntos
/genética , MicroRNAs/imunologia , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia , Infecções Bacterianas/terapia , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , /parasitologia , MicroRNAs/genética , MicroRNAs/uso terapêutico , Doenças Parasitárias/imunologia , Doenças Parasitárias/terapia , Transdução de Sinais , Viroses/genética , Viroses/imunologia , Viroses/terapia
15.
Sci China Life Sci ; 56(1): 13-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23269554

RESUMO

The innate immune response provides the initial defense against infection. This is accomplished by families of pattern recognition receptors (PRRs) that bind to conserved molecules in bacteria, fungi and viruses. PRRs are finely regulated by elaborate mechanisms to ensure a beneficial outcome in response to foreign invaders. MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that are emerging as important regulators in immune responses at the post-transcriptional level, through the inhibition of translation, or by inducing mRNA degradation. It has been shown that miRNAs have unique expression profiles in cells of the innate immune systems and play pivotal roles in regulating the signal pathways of innate receptors, including Toll-like receptors, RIG-I-like receptors and Nod-like receptors. We have summarized the recent literature providing new insights into the regulation of innate receptor pathways by miRNAs.


Assuntos
Imunidade Inata/imunologia , MicroRNAs/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Transdução de Sinais/imunologia , Proteína DEAD-box 58 , RNA Helicases DEAD-box/imunologia , Humanos , Proteína Adaptadora de Sinalização NOD1/imunologia , Receptores Toll-Like/imunologia
16.
Cell Mol Immunol ; 10(1): 65-71, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23262976

RESUMO

The innate immune system recognizes invading pathogens through germline-encoded pattern recognition receptors (PRRs), which elicit innate antimicrobial and inflammatory responses and initiate adaptive immunity to control or eliminate infection. Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I) are the key innate immune PRRs and are tightly regulated by elaborate mechanisms to ensure a beneficial outcome in response to foreign invaders. Although much of the focus in the literature has been on the study of protein regulators of inflammation, microRNAs (miRNAs) have emerged as important controllers of certain features of the inflammatory process. Several miRNAs are induced by TLR and RIG-I activation in myeloid cells and act as feedback regulators of TLR and RIG-I signaling. In this review, we comprehensively discuss the recent understanding of how miRNA networks respond to TLR and RIG-I signaling and their role in the initiation and termination of inflammatory responses. Increasing evidence also indicates that both virus-encoded miRNAs and cellular miRNAs have important functions in viral replication and host anti-viral immunity.


Assuntos
RNA Helicases DEAD-box/imunologia , Imunidade Inata , MicroRNAs/imunologia , Células Mieloides/imunologia , Transdução de Sinais/imunologia , Receptores Toll-Like/imunologia , Animais , Proteína DEAD-box 58 , Humanos , Inflamação/imunologia , Inflamação/patologia , Células Mieloides/patologia , Células Mieloides/virologia , RNA Viral/imunologia , Viroses/imunologia , Viroses/patologia , Viroses/virologia , Fenômenos Fisiológicos Virais/imunologia , Replicação Viral/imunologia , Vírus
17.
Cell Mol Immunol ; 9(6): 497-502, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23042536

RESUMO

Effective recognition of viral infections and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs (miRNAs). A previous study showed that miR-466l upregulates IL-10 expression in macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation. However, the ability of miR-466l to regulate antiviral immune responses remains unknown. Here, we found that interferon-alpha (IFN-α) expression was repressed in Sendai virus (SeV)- and vesicular stomatitis virus (VSV)-infected macrophages and in dendritic cells transfected with miR-466l expression. Moreover, multiple IFN-α species can be directly targeted by miR-466l through their 3' untranslated region (3'UTR). This study has demonstrated that miR-466l could directly target IFN-α expression to inhibit host antiviral innate immune response.


Assuntos
Imunidade Inata/imunologia , Interferon-alfa/metabolismo , RNA Mensageiro/metabolismo , Vírus Sendai/imunologia , Vesiculovirus/imunologia , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Células Dendríticas/imunologia , Células Dendríticas/virologia , Regulação da Expressão Gênica , Células HEK293 , Humanos , Interferon-alfa/biossíntese , Interferon-alfa/genética , Macrófagos/imunologia , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs , RNA Mensageiro/genética , Transcrição Genética , Replicação Viral/imunologia
18.
Nephrology (Carlton) ; 14(6): 573-80, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19712257

RESUMO

AIM: To find out if a single dose of glutamine can relieve acute renal ischaemia-reperfusion injury in rats, to explore the role of heat shock protein in this process. METHODS: Forty-eight Sprague-Dawley rats were assigned to four groups: saline as control group; glutamine group; quercetin (heat shock protein inhibitor) plus glutamine group; and quercetin plus saline group. The renal ischaemia-reperfusion rat model was established 1 h after drug administration. Serum creatinine (CR) and blood urea nitrogen (BUN) were analyzed. The kidneys were harvested to evaluate the degree of renal injuries. Heat shock protein expression was detected by immunohistochemistry and western blot. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and apoptosis index was calculated. RESULTS: Statistical data from CR, BUN, haematoxylin-eosin (HE) dyeing and TUNEL assay results showed that ischaemia-reperfusion injury and cell apoptosis in the glutamine group were significantly milder than those in control group (P < 0.05), while ischaemia-reperfusion injury and cell apoptosis in the quercetin plus glutamine group and quercetin plus saline group were more severe than those in the control group (P < 0.05). Statistical data from immunohistochemistry and western blot results showed that heat shock protein expression was enhanced in the glutamine group compared with that in the control group (P < 0.01), while it was weaker in the quercetin plus glutamine group and quercetin plus saline group than that in the control group (P < 0.01). CONCLUSION: Our experiment suggested that a single dose of glutamine could relieve renal ischaemia-reperfusion injury in rats in 24 h, and its mechanism may be associated with enhanced heat shock protein expression. This finding may provide a new alternative for protecting against clinical renal ischaemia-reperfusion injury.


Assuntos
Glutamina/farmacologia , Proteínas de Choque Térmico/fisiologia , Rim/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Proteínas de Choque Térmico/análise , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley
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