Base de dados : MEDLINE
Pesquisa : A11.329.372.588 [Categoria DeCS]
Referências encontradas : 5346 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 535 ir para página                         

  1 / 5346 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28450389
[Au] Autor:Triantafyllou E; Pop OT; Possamai LA; Wilhelm A; Liaskou E; Singanayagam A; Bernsmeier C; Khamri W; Petts G; Dargue R; Davies SP; Tickle J; Yuksel M; Patel VC; Abeles RD; Stamataki Z; Curbishley SM; Ma Y; Wilson ID; Coen M; Woollard KJ; Quaglia A; Wendon J; Thursz MR; Adams DH; Weston CJ; Antoniades CG
[Ad] Endereço:Institute of Liver Studies, King's College Hospital, King's College London, London, UK.
[Ti] Título:MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure.
[So] Source:Gut;67(2):333-347, 2018 02.
[Is] ISSN:1468-3288
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and liver inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown. Here, we aimed to investigate the impact of Mer tyrosine kinase (MerTK) during ALF and also examine how the microenvironmental mediator, secretory leucocyte protease inhibitor (SLPI), governs this response. DESIGN: Flow cytometry, immunohistochemistry, confocal imaging and gene expression analyses determined the phenotype, functional/transcriptomic profile and tissue topography of MerTK+ monocytes/macrophages in ALF, healthy and disease controls. The temporal evolution of macrophage MerTK expression and its impact on resolution was examined in APAP-induced acute liver injury using wild-type (WT) and Mer-deficient (Mer ) mice. SLPI effects on hepatic myeloid cells were determined in vitro and in vivo using APAP-treated WT mice. RESULTS: We demonstrate a significant expansion of resolution-like MerTK+HLA-DR cells in circulatory and tissue compartments of patients with ALF. Compared with WT mice which show an increase of MerTK+MHCII macrophages during the resolution phase in ALF, APAP-treated Mer mice exhibit persistent liver injury and inflammation, characterised by a decreased proportion of resident Kupffer cells and increased number of neutrophils. Both in vitro and in APAP-treated mice, SLPI reprogrammes myeloid cells towards resolution responses through induction of a MerTK+HLA-DR phenotype which promotes neutrophil apoptosis and their subsequent clearance. CONCLUSIONS: We identify a hepatoprotective, MerTK+, macrophage phenotype that evolves during the resolution phase following ALF and represents a novel immunotherapeutic target to promote resolution responses following acute liver injury.
[Mh] Termos MeSH primário: Falência Hepática Aguda/imunologia
Falência Hepática Aguda/metabolismo
Macrófagos/metabolismo
Inibidor Secretado de Peptidases Leucocitárias/farmacologia
c-Mer Tirosina Quinase/metabolismo
[Mh] Termos MeSH secundário: Acetaminofen
Adulto
Idoso
Animais
Estudos de Casos e Controles
Feminino
Expressão Gênica
Genes MHC Classe II
Antígenos HLA-DR/metabolismo
Seres Humanos
Macrófagos do Fígado/imunologia
Macrófagos do Fígado/metabolismo
Falência Hepática Aguda/induzido quimicamente
Falência Hepática Aguda/patologia
Macrófagos/imunologia
Masculino
Camundongos
Meia-Idade
Monócitos/imunologia
Monócitos/metabolismo
Neutrófilos/fisiologia
Fenótipo
Inibidor Secretado de Peptidases Leucocitárias/metabolismo
Inibidor Secretado de Peptidases Leucocitárias/uso terapêutico
Transcriptoma
c-Mer Tirosina Quinase/deficiência
c-Mer Tirosina Quinase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HLA-DR Antigens); 0 (Secretory Leukocyte Peptidase Inhibitor); 362O9ITL9D (Acetaminophen); EC 2.7.10.1 (MERTK protein, human); EC 2.7.10.1 (Mertk protein, mouse); EC 2.7.10.1 (c-Mer Tyrosine Kinase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1136/gutjnl-2016-313615


  2 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29305862
[Au] Autor:Li Y; Lou C; Wang W
[Ad] Endereço:Department of Pediatrics, Huaihe Hospital, Henan University, Kaifeng 475000, China. Electronic address: liyanyanghuaihe@qq.com.
[Ti] Título:STIM1 deficiency protects the liver from ischemia/reperfusion injury in mice.
[So] Source:Biochem Biophys Res Commun;496(2):422-428, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatic ischemia reperfusion (I/R) injury is unavoidable in various clinical conditions. Despite considerable investigation, the underlying molecular mechanism revealing liver I/R injury remains elusive. Stromal interaction molecule 1 (STIM1) plays essential role in regulating the induction of cellular responses to a number of stress conditions, including temperature changes, elevated ROS, and hypoxia. Here, to explore if STIM1 is involved in hepatic injury, wild type (WT) and STIM1-knockout (STIM1 ) mice were subjected to I/R. Our results indicated that the WT mice with hepatic I/R injury showed higher STIM1 expressions from gene and protein levels in liver tissue samples. Similar results were observed in hypoxia-exposed cells in vitro. Significantly, STIM1 attenuated hepatic injury compared to the WT mice after I/R, as evidenced by the improved pathological alterations in liver sections. WT mice subjected to liver I/R showed higher serum alanine aminotransferase (ALT) and aminotransferase (AST) levels, as well as pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß, which were significantly reduced by STIM1 . In addition, STIM1 also decreased the liver mRNA levels of pro-inflammatory cytokines in mice after I/R injury. Furthermore, significantly decreased oxidative stress was found in STIM1 mice after I/R injury compared to the WT group of mice, evidenced by the enhanced superoxide dismutase (SOD) activity and the reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels in liver tissue samples. Moreover, STIM1 mice with hepatic I/R injury displayed the down-regulated nuclear factor of activated T cell (NFAT1), Orai1 and cleaved Caspase-3 levels in liver, contributing to apoptosis suppression. The results above were confirmed in hypoxia-treated cells lacking of STIM1 expression. Together, the findings suggested that STIM1-deletion protects the liver from I/R injury in mice through inhibiting inflammation, oxidative stress and apoptosis. STIM1 could be considered as a potential therapeutic target to ameliorate I/R injury.
[Mh] Termos MeSH primário: Macrófagos do Fígado/metabolismo
Fígado/metabolismo
Traumatismo por Reperfusão/genética
Molécula 1 de Interação Estromal/genética
[Mh] Termos MeSH secundário: Alanina Transaminase/sangue
Animais
Apoptose/genética
Aspartato Aminotransferases/sangue
Caspase 3/genética
Caspase 3/metabolismo
Regulação da Expressão Gênica
Interleucina-1beta/genética
Interleucina-1beta/metabolismo
Interleucina-6/genética
Interleucina-6/metabolismo
Macrófagos do Fígado/patologia
Fígado/patologia
Masculino
Malondialdeído/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fatores de Transcrição NFATC/genética
Fatores de Transcrição NFATC/metabolismo
Proteína ORAI1/genética
Proteína ORAI1/metabolismo
Estresse Oxidativo
Cultura Primária de Células
Espécies Reativas de Oxigênio/metabolismo
Traumatismo por Reperfusão/metabolismo
Traumatismo por Reperfusão/patologia
Traumatismo por Reperfusão/prevenção & controle
Molécula 1 de Interação Estromal/deficiência
Superóxido Dismutase/genética
Superóxido Dismutase/metabolismo
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL1B protein, mouse); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (NFATC Transcription Factors); 0 (Nfatc2 protein, mouse); 0 (ORAI1 Protein); 0 (Orai1 protein, mouse); 0 (Reactive Oxygen Species); 0 (Stim1 protein, mouse); 0 (Stromal Interaction Molecule 1); 0 (Tumor Necrosis Factor-alpha); 4Y8F71G49Q (Malondialdehyde); EC 1.15.1.1 (Superoxide Dismutase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 3.4.22.- (Casp3 protein, mouse); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


  3 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28458361
[Au] Autor:Nagano T; Nagano K; Nabeshi H; Yoshida T; Kamada H; Tsunoda SI; Gao JQ; Higashisaka K; Yoshioka Y; Tsutsumi Y
[Ad] Endereço:Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University.
[Ti] Título:Modifying the Surface of Silica Nanoparticles with Amino or Carboxyl Groups Decreases Their Cytotoxicity to Parenchymal Hepatocytes.
[So] Source:Biol Pharm Bull;40(5):726-728, 2017.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We previously reported that unmodified silica nanoparticles with diameters of 70 nm (nSP70) induced liver damage in mice, whereas nSP70 modified with carboxyl or amino groups did not. In addition, we have found that both unmodified and modified nSP70s localize in both Kupffer cells and parenchymal hepatocytes. We therefore evaluated the contributions of nSP70 uptake by these cell populations to liver damage. To this end, we pretreated mice with gadolinium (III) chloride hydrate (GdCl ) to prevent nSP70 uptake by Kupffer cells, subsequently injected the mice with either type of nSP70, and then assessed plasma levels of alanine aminotransferase (ALT). In mice given GdCl , unmodified nSP70 increased ALT levels. From these data, we hypothesized that in GdCl -treated mice, the unmodified nSP70 that was prevented from entering Kupffer cells was shunted to parenchymal hepatocytes, where it induced cytotoxicity and increased liver damage. In contrast, GdCl pretreatment had no effect on ALT levels in mice injected with surface-modified nSP70s, suggesting that modified nSP70s spared parenchymal hepatocytes and thus induced negligible liver damage. In cytotoxicity analyses, the viability of a parenchymal hepatocyte line was greater when exposed to surface-modified nSP70s than to unmodified nSP70s. These findings imply that the decreased liver damage associated with surface-modified compared with unmodified nSP70 is attributable to decreased cytotoxicity to parenchymal hepatocytes.
[Mh] Termos MeSH primário: Aminas/química
Ácidos Carboxílicos/química
Nanopartículas/química
Dióxido de Silício/química
[Mh] Termos MeSH secundário: Alanina Transaminase/análise
Animais
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Doença Hepática Induzida por Substâncias e Drogas/enzimologia
Doença Hepática Induzida por Substâncias e Drogas/patologia
Feminino
Gadolínio/química
Hepatócitos/efeitos dos fármacos
Macrófagos do Fígado/efeitos dos fármacos
Testes de Função Hepática
Camundongos
Camundongos Endogâmicos BALB C
Nanopartículas/toxicidade
Tamanho da Partícula
Dióxido de Silício/toxicidade
Propriedades de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amines); 0 (Carboxylic Acids); 7631-86-9 (Silicon Dioxide); AU0V1LM3JT (Gadolinium); EC 2.6.1.2 (Alanine Transaminase); P7082WY76D (gadolinium chloride)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00917


  4 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29369172
[Au] Autor:Wu Y; Ding J; Sun Q; Zhou K; Zhang W; Du Q; Xu T; Xu W
[Ad] Endereço:Infectious Disease, Ruian People's Hospital, Ruian, Zhejiang Province, P.R. China.
[Ti] Título:Long noncoding RNA hypoxia-inducible factor 1 alpha-antisense RNA 1 promotes tumor necrosis factor-α-induced apoptosis through caspase 3 in Kupffer cells.
[So] Source:Medicine (Baltimore);97(4):e9483, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Kupffer cells (KCs) play a crucial role in the pathogenesis of acute-on-chronic liver failure (ACLF) which is characterized by acute and severe disease in patients with preexisting liver disease and shows high mortality. Long noncoding RNAs (lncRNAs) are recently found to be involved in gene regulation. However, the mechanisms of how KCs are regulated by inflammatory factors, tumor necrosis factor-α (TNF-α), and whether lncRNAs are involved in the process remain largely unknown. Hence, we investigated the role of lncRNAs in the cytotoxicity of TNF-α on KCs.lncRNA array (The lncRNAs in the array are apoptosis-related lncRNAs reported in some research papers.) was used to identify lncRNAs related with liver fibrosis. Annexin V/protease inhibitor (PI) staining was used for detection of cell apoptosis. Real time-polymerase chain reaction was utilized for analysis of mRNA levels of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 1 (HIF1A-AS1) and apoptosis-related genes. Western blot was implied to the determination of lymphoid enhancer factor-1 (LEF-1).In this study, we found that HIF1A-AS1 could be upregulated by TNF-α by lncRNA array analysis and knockdown of HIF1A-AS1 significantly rescued cell apoptosis induced by TNF-α. Moreover, inhibition of HIF1A-AS1 markedly reduced mRNA level of caspase 3 which can be significantly enhanced by TNF-α. Furthermore, HIF1A-AS1 showed binding sites for LEF-1 and siRNA-mediated downregulation of LEF-1 decreased HIF1A-AS1 level in KCs treated with TNF-α.This study elucidates a new role of HIF1A-AS1 in TNF-α-induced cell apoptosis and provides potential therapeutic targets for ACLF.
[Mh] Termos MeSH primário: Apoptose/genética
Fator 1 Induzível por Hipóxia/genética
Macrófagos do Fígado/metabolismo
RNA Longo não Codificante/fisiologia
Fator de Necrose Tumoral alfa/fisiologia
[Mh] Termos MeSH secundário: Insuficiência Hepática Crônica Agudizada/genética
Caspase 3/fisiologia
Técnicas de Cultura de Células
Seres Humanos
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoxia-Inducible Factor 1); 0 (RNA, Long Noncoding); 0 (Tumor Necrosis Factor-alpha); 0 (long non-coding RNA HIF 1alpha-anti-sense 1, human); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009483


  5 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27770461
[Au] Autor:Piao X; Yamazaki S; Komazawa-Sakon S; Miyake S; Nakabayashi O; Kurosawa T; Mikami T; Tanaka M; Van Rooijen N; Ohmuraya M; Oikawa A; Kojima Y; Kakuta S; Uchiyama Y; Tanaka M; Nakano H
[Ad] Endereço:Department of Biochemistry, Toho University School of Medicine, Tokyo, Japan.
[Ti] Título:Depletion of myeloid cells exacerbates hepatitis and induces an aberrant increase in histone H3 in mouse serum.
[So] Source:Hepatology;65(1):237-252, 2017 01.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar ) mice. Cellular FLICE-inhibitory protein expression was down-regulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis. Cflar mice developed acute hepatitis and recovered with clearance of apoptotic hepatocytes at 24 hours after injection of low doses of tumor necrosis factor α (TNFα), which could not induce hepatitis in wild-type (WT) mice. Depletion of Kupffer cells (KCs) by clodronate liposomes did not impair clearance of dying hepatocytes or exacerbate hepatitis in Cflar mice. To elucidate the roles of BM-derived monocytes and neutrophils in clearance of apoptotic hepatocytes, we examined the effect of depletion of these cells on TNFα-induced hepatitis in Cflar mice. We reconstituted Cflar mice with BM cells from transgenic mice in which human diphtheria toxin receptor (DTR) was expressed under control of the lysozyme M (LysM) promoter. TNFα-induced infiltration of myeloid cells, including monocytes and neutrophils, was completely ablated in LysM-DTR BM-reconstituted Cflar mice pretreated with diphtheria toxin, whereas KCs remained present in the livers. Under these experimental conditions, LysM-DTR BM-reconstituted Cflar mice rapidly developed severe hepatitis and succumbed within several hours of TNFα injection. We found that serum interleukin-6 (IL-6), TNFα, and histone H3 were aberrantly increased in LysM-DTR BM-reconstituted, but not in WT BM-reconstituted, Cflar mice following TNFα injection. CONCLUSION: These findings indicate an unexpected role of myeloid cells in decreasing serum IL-6, TNFα, and histone H3 levels via the suppression of TNFα-induced hepatocyte apoptosis. (Hepatology 2017;65:237-252).
[Mh] Termos MeSH primário: Hepatite/sangue
Hepatite/etiologia
Histonas/sangue
Células Mieloides/fisiologia
[Mh] Termos MeSH secundário: Animais
Apoptose
Progressão da Doença
Hepatócitos
Macrófagos do Fígado
Camundongos
Camundongos Transgênicos
Fator de Necrose Tumoral alfa/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Histones); 0 (Tumor Necrosis Factor-alpha)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1002/hep.28878


  6 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29045904
[Au] Autor:Liew PX; Lee WY; Kubes P
[Ad] Endereço:Snyder institute of Chronic Diseases, University of Calgary, Calgary, Canada.
[Ti] Título:iNKT Cells Orchestrate a Switch from Inflammation to Resolution of Sterile Liver Injury.
[So] Source:Immunity;47(4):752-765.e5, 2017 Oct 17.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:After traumatic injury, some cells function as detectors to sense injury and to modulate the local immune response toward a restitution phase by affecting the local cytokine milieu. Using intravital microscopy, we observed that patrolling invariant natural killer T (iNKT) cells were initially excluded from a site of hepatic injury but subsequently were strategically arrested first via self-antigens and then by cytokines, circumscribing the injured site at exactly the location where monocytes co-localized and hepatocytes proliferated. Activation of iNKT cells by self-antigens resulted in the production of interleukin-4 (IL-4) but not interferon-γ (IFN-γ). This promoted increased hepatocyte proliferation, monocyte transition (from Ly6C to Ly6C ), and improved healing where IL-4 from iNKT cells was critical for these processes. Disruption of any of these mechanisms led to delayed wound healing. We have shown that self-antigen-driven iNKT cells function as sensors and orchestrators of the transformation from inflammation to tissue restitution for essential timely wound repair.
[Mh] Termos MeSH primário: Hepatócitos/imunologia
Inflamação/imunologia
Fígado/imunologia
Células T Matadoras Naturais/imunologia
[Mh] Termos MeSH secundário: Animais
Autoantígenos/imunologia
Proliferação Celular
Hepatócitos/metabolismo
Hepatócitos/patologia
Interleucina-4/genética
Interleucina-4/imunologia
Interleucina-4/metabolismo
Macrófagos do Fígado/imunologia
Fígado/lesões
Fígado/metabolismo
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Transgênicos
Microscopia Confocal
Microscopia de Fluorescência por Excitação Multifotônica
Monócitos/imunologia
Fatores de Tempo
Cicatrização/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantigens); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE


  7 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28965953
[Au] Autor:Ge CX; Qin YT; Lou DS; Li Q; Li YY; Wang ZM; Yang WW; Wang M; Liu N; Wang Z; Zhang PX; Tu YY; Tan J; Xu MX
[Ad] Endereço:College of Engineering and Applied Sciences, Nanjing University, Nanjing, 210023, PR China; School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 400067, PR China.
[Ti] Título:iRhom2 deficiency relieves TNF-α associated hepatic dyslipidemia in long-term PM2.5-exposed mice.
[So] Source:Biochem Biophys Res Commun;493(4):1402-1409, 2017 Dec 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Accumulating researches reported that particulate matter (PM2.5) is a risk factor for developing various diseases, including metabolic syndrome. Recently, inactive rhomboid protein 2 (iRhom2) was considered as a necessary modulator for shedding of tumor necrosis factor-α (TNF-α) in immune cells. TNF-α, a major pro-inflammatory cytokine, was linked to various pathogenesis of diseases, including dyslipidemia. Here, wild type (WT) and iRhom2-knockout (iRhom2 ) mice were used to investigate the effects of iRhom2 on PM2.5-induced hepatic dyslipidemia. The hepatic histology, inflammatory response, glucose tolerance, serum parameters and gene expressions were analyzed. We found that long-term inhalation of PM2.5 resulted in hepatic steatosis. And a significant up-regulation of iRhom2 in liver tissues was observed, accompanied with elevated TNF-α, TNF-α converting enzyme (TACE), TNFα receptor (TNFR)2 and various inflammatory cytokines expressions. Additionally, PM2.5 treatment caused TG and TC accumulation in serum and liver, probably attributed to changes of genes modulating lipid metabolism. Intriguingly, hepatic injury and dyslipidemia were attenuated by iRhom2 in mice with PM2.5 challenge. In vitro, iRhom2-knockdwon reduced TNF-α expressions and its associated inflammatory cytokines in Kupffer cells, implying that liver-resident macrophages played an important role in regulating hepatic inflammation and lipid metabolism in cells treated with PM2.5. The findings indicated that long-term PM2.5 exposure caused hepatic steatosis and dyslipidemia through triggering inflammation, which was, at least partly, dependent on iRhom2/TNF-α pathway in liver-resident macrophages.
[Mh] Termos MeSH primário: Proteínas de Transporte/metabolismo
Dislipidemias/etiologia
Dislipidemias/metabolismo
Fígado Gorduroso/etiologia
Fígado Gorduroso/metabolismo
Material Particulado/toxicidade
Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Poluentes Atmosféricos/toxicidade
Animais
Proteínas de Transporte/genética
Linhagem Celular
Dislipidemias/genética
Fígado Gorduroso/genética
Mediadores da Inflamação/metabolismo
Macrófagos do Fígado/metabolismo
Metabolismo dos Lipídeos/genética
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Material Particulado/administração & dosagem
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transdução de Sinais
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Air Pollutants); 0 (Carrier Proteins); 0 (Inflammation Mediators); 0 (Particulate Matter); 0 (RNA, Messenger); 0 (Tumor Necrosis Factor-alpha); 0 (iRhom2 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE


  8 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28882574
[Au] Autor:Zhao YY; Yang R; Xiao M; Guan MJ; Zhao N; Zeng T
[Ad] Endereço:Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, PR China.
[Ti] Título:Kupffer cells activation promoted binge drinking-induced fatty liver by activating lipolysis in white adipose tissues.
[So] Source:Toxicology;390:53-60, 2017 Sep 01.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Kupffer cells (KCs) have been suggested to play critical roles in chronic ethanol induced early liver injury, but the role of KCs in binge drinking-induced hepatic steatosis remains unclear. This study was designed to investigate the roles of KCs inhibitor (GdCl ) and TNF-α antagonist (etanercept) on binge drinking-induced liver steatosis and to explore the underlying mechanisms. C57BL/6 mice were exposed to three doses of ethanol (6g/kg body weight) to mimic binge drinking-induced fatty liver. The results showed that both GdCl and etanercept partially but significantly alleviated binge drinking-induced increase of hepatic triglyceride (TG) level, and reduced fat droplets accumulation in mice liver. GdCl but not etanercept significantly blocked binge drinking-induced activation of KCs. However, neither GdCl nor etanercept could affect binge drinking-induced decrease of PPAR-α, ACOX, FAS, ACC and SCD protein levels, or increase of the LC3 II/LC3 I ratio and p62 protein level. Interestingly, both GdCl and etanercept significantly suppressed binge drinking-induced phosphorylation of HSL in epididymal adipose tissues. Results of in vitro studies with cultured epididymal adipose tissues showed that TNF-α could increase the phosphorylation of HSL in adipose tissues and upgrade the secretion of free fatty acid (FFA) in the culture medium. Taken together, KCs inhibitor and TNF-α antagonist could partially attenuate binge drinking-induced liver steatosis, which might be attributed to the suppression of mobilization of white adipose tissues. These results suggest that KCs activation may promote binge drinking-induced fatty liver by TNF-α mediated activation of lipolysis in white adipose tissues.
[Mh] Termos MeSH primário: Tecido Adiposo Branco/metabolismo
Bebedeira
Etanol
Fígado Gorduroso Alcoólico/metabolismo
Macrófagos do Fígado/metabolismo
Lipólise
Fígado/metabolismo
[Mh] Termos MeSH secundário: Tecido Adiposo Branco/efeitos dos fármacos
Tecido Adiposo Branco/patologia
Animais
Autofagia/efeitos dos fármacos
Modelos Animais de Doenças
Etanercepte/farmacologia
Fígado Gorduroso Alcoólico/etiologia
Fígado Gorduroso Alcoólico/patologia
Fígado Gorduroso Alcoólico/prevenção & controle
Gadolínio/farmacologia
Macrófagos do Fígado/efeitos dos fármacos
Macrófagos do Fígado/patologia
Gotículas Lipídicas/metabolismo
Lipogênese/efeitos dos fármacos
Lipólise/efeitos dos fármacos
Fígado/efeitos dos fármacos
Fígado/patologia
Masculino
Camundongos Endogâmicos C57BL
PPAR alfa/genética
PPAR alfa/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Técnicas de Cultura de Tecidos
Triglicerídeos/metabolismo
Fator de Necrose Tumoral alfa/antagonistas & inibidores
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (PPAR alpha); 0 (Srebf1 protein, mouse); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Triglycerides); 0 (Tumor Necrosis Factor-alpha); 3K9958V90M (Ethanol); AU0V1LM3JT (Gadolinium); OP401G7OJC (Etanercept); P7082WY76D (gadolinium chloride)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE


  9 / 5346 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28815688
[Au] Autor:Canali S; Wang CY; Zumbrennen-Bullough KB; Bayer A; Babitt JL
[Ad] Endereço:Program in Anemia Signaling Research, Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
[Ti] Título:Bone morphogenetic protein 2 controls iron homeostasis in mice independent of Bmp6.
[So] Source:Am J Hematol;92(11):1204-1213, 2017 Nov.
[Is] ISSN:1096-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody. Moreover, BMP2/4 antibody inhibits hepcidin expression and induces iron loading in wildtype mice, whereas a BMP4 antibody has no effect. Bmp2 mRNA is predominantly expressed in endothelial cells of the liver, where its baseline expression is higher, but its induction by iron is less robust than Bmp6. Mice with a conditional ablation of Bmp2 in endothelial cells exhibit hepcidin deficiency, serum iron overload, and tissue iron loading in liver, pancreas and heart, with reduced spleen iron. Together, these data demonstrate that in addition to BMP6, endothelial cell BMP2 has a non-redundant role in hepcidin regulation by iron.
[Mh] Termos MeSH primário: Proteína Morfogenética Óssea 2/metabolismo
Proteína Morfogenética Óssea 6/metabolismo
Homeostase
Ferro/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/farmacologia
Proteína Morfogenética Óssea 2/antagonistas & inibidores
Proteína Morfogenética Óssea 2/genética
Proteína Morfogenética Óssea 4/antagonistas & inibidores
Proteína Morfogenética Óssea 6/genética
Células Endoteliais/efeitos dos fármacos
Células Endoteliais/metabolismo
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Hepatócitos/metabolismo
Hepcidinas/genética
Hepcidinas/metabolismo
Ferro/sangue
Sobrecarga de Ferro/genética
Sobrecarga de Ferro/metabolismo
Sobrecarga de Ferro/patologia
Macrófagos do Fígado/metabolismo
Fígado/efeitos dos fármacos
Fígado/metabolismo
Masculino
Camundongos
Camundongos Knockout
Fosforilação
Proteína Smad1/metabolismo
Proteína Smad5/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Bone Morphogenetic Protein 2); 0 (Bone Morphogenetic Protein 4); 0 (Bone Morphogenetic Protein 6); 0 (Hepcidins); 0 (Smad1 Protein); 0 (Smad5 Protein); E1UOL152H7 (Iron)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1002/ajh.24888


  10 / 5346 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28813662
[Au] Autor:Sierro F; Evrard M; Rizzetto S; Melino M; Mitchell AJ; Florido M; Beattie L; Walters SB; Tay SS; Lu B; Holz LE; Roediger B; Wong YC; Warren A; Ritchie W; McGuffog C; Weninger W; Le Couteur DG; Ginhoux F; Britton WJ; Heath WR; Saunders BM; McCaughan GW; Luciani F; MacDonald KPA; Ng LG; Bowen DG; Bertolino P
[Ad] Endereço:Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: frederis@ansto.gov.au.
[Ti] Título:A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.
[So] Source:Immunity;47(2):374-388.e6, 2017 Aug 15.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.
[Mh] Termos MeSH primário: Macrófagos do Fígado/fisiologia
Listeria monocytogenes/imunologia
Listeriose/imunologia
Fígado/imunologia
Macrófagos/imunologia
Neutrófilos/imunologia
Peritônio/microbiologia
[Mh] Termos MeSH secundário: Animais
Comunicação Celular
Autorrenovação Celular
Interações Hospedeiro-Patógeno
Seres Humanos
Imunidade Inata
Macrófagos do Fígado/microbiologia
Fígado/microbiologia
Fígado/patologia
Macrófagos/microbiologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Monócitos/imunologia
Infiltração de Neutrófilos
Peritônio/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE



página 1 de 535 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde