Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.233
Filtrar
1.
Exp Parasitol ; 204: 107725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306646

RESUMO

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.


Assuntos
Imunidade Celular , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/parasitologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos CBA , Óvulo/imunologia , Contagem de Ovos de Parasitas , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Caramujos/parasitologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia
2.
Folia Histochem Cytobiol ; 57(2): 74-83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31187872

RESUMO

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease which becomes a rapidly growing health problem in the Western countries. The development of the disease is most often connected to obesity. NAFLD is also considered as the hepatic manifestation of metabolic syndrome. Transforming growth factor b1 (TGF-b1) plays an important role in the pathogenesis of liver fibrosis, being involved in activation of hepatic stellate cells, stimulation of collagen gene transcription, and suppression of matrix metalloproteinase expression. The objective of the study was to evaluate by immunohistochemistry the expression of TGF-b1 in the liver tissue of NAFLD patients and correlate it with anthropometric, biochemical and routine histological parameters. MATERIAL AND METHODS: The study group consisted of 48 patients with diagnosed NAFLD. Liver steatosis, NAFLD Activity Score (NAS) and METAVIR score of fibrosis were evaluated in liver biopsies. The immunoreactivity of TGF-b1 was evaluated semi-quantitatively separately in portal, septal, lobular hepatocytic and lobular sinu-soidal liver compartments. The results were analyzed in regard to patients' clinical and biochemical parameters. RESULTS: Neither steatosis nor NAS correlated with TGF-b1 expression in any liver compartment, whereas METAVIR score of fibrosis was associated with increased immunoreactivity of TGF-b1 in most of the studied liver compartments. TGF-b1 immunoreactivity showed positive correlation with patients' age and its expression in septal compartment disclosed positive correlation with body mass index, and waist and hip circumference. Hyaluronic acid serum level was positively and iron concentration was negatively associated with TGF-b1 ex-pression in the selected consecutive liver compartments. CONCLUSIONS: The immunohistochemical expression of TGF-b1 may be complementary to routine methods of liver fibrosis evaluation.


Assuntos
Cirrose Hepática/imunologia , Fígado/imunologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Fator de Crescimento Transformador beta1/imunologia , Adulto , Peptídeo C/sangue , Fígado Gorduroso/patologia , Feminino , Hemoglobina A Glicada/análise , Haptoglobinas/análise , Humanos , Ácido Hialurônico/sangue , Imuno-Histoquímica , Ferro/sangue , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Fator de Crescimento Transformador beta1/sangue
3.
Environ Pollut ; 246: 963-971, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159146

RESUMO

Bisphenol S (BPS) has been widely used as a bisphenol alternative in recent few years. However, with mounting evidence suggesting that the presence of BPS in the environment also poses risks to ecosystems and human health, we decided to use the juvenile common carp (Cyprinus carpio) and its primary macrophages as in vivo and in vitro models to examine if BPS is a safe substitute of BPA. The present study evaluated the immune responses of chronic BPS exposure and their mechanisms of action associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway. Potential oxidative stress and pro-inflammatory effects of BPS exposure were identified in fish liver after 60-day exposure, based on the increased reactive oxygen species (ROS) production, antioxidant capacity, NO production, lipid peroxidation, and induction of inflammatory cytokine expression, as well as acute phase protein levels of C-reactive protein, immunoglobulin M, lysozyme, and complement component 3. Moreover, pparγ, PPAR pathway-associated genes retinoid x receptor α (rxrα) and nuclear factor-κb (nfκb) presented a rough concentration-dependent alteration after BPS exposure. An acute BPS exposure to the isolated primary macrophages from juvenile common carp was performed to help elucidate gene expression patterns of pparγ, rxrα, and nfκb in a typical immune cell model, the results were consistent with what we found in vivo experiments for long-term BPS exposure. Furthermore, with coexposure to BPS and a PPARγ antagonist, the restriction of PPAR signaling pathway significantly inhibited the induction of ROS and the mRNA level of interleukin-1ß, confirming the involvement of PPAR pathway in BPS-induced chronic inflammatory stress in liver.


Assuntos
Poluentes Ambientais/toxicidade , Inflamação/metabolismo , Fígado/efeitos dos fármacos , PPAR gama/metabolismo , Fenóis/toxicidade , Sulfonas/toxicidade , Animais , Carpas/imunologia , Carpas/metabolismo , Inflamação/genética , Fígado/imunologia , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
4.
Zhonghua Gan Zang Bing Za Zhi ; 27(4): 241-243, 2019 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-31082332

RESUMO

The mechanism of innate and adaptive immune responses to chronic infections with hepatotropic viruses (HBV, HCV) was studied in 2018. Its mechanism elucidated the dysregulation of natural killer (NK) cells, monocytes, B cells and T cells. In addition, a new target for immune regulation of HBV infection (TLR3/OX40L) was introduced. The discovery of new NK cell immune checkpoints, the involvement of mononuclear macrophages in liver failure and inflammation, sex hormone affecting intrahepatic-resistant bacterial infection through the regulation of humoral immunity, and the communication mechanism between liver and other immune organs have enriched people's understanding of liver immunology and its clinical significance.


Assuntos
Hepatite A/imunologia , Hepatovirus/imunologia , Células Matadoras Naturais , Fígado/imunologia , Humanos , Linfócitos T
5.
Life Sci ; 228: 266-273, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31077717

RESUMO

Sitagliptin is an oral hypoglycemic drug that acts by selective inhibition of dipeptidyl peptidase-4 (DDP-4) enzyme. AIM: This study scrutinized the hepatoprotective impact of sitagliptin) against thioacetamide (TAA)-induced liver damage in mice. MAIN METHODS: Male mice were injected with TAA (500 mg/kg) then treated with sitagliptin (20 mg/kg) orally for 5 days. KEY FINDINGS: Histopathological results of TAA group revealed severe degree of centrolobular hepatic necrosis. Additionally, biochemical findings showed marked elevation in the serum transaminases and gamma glutamyl transpeptidase (GGT) levels in TAA group. Injection of TAA significantly disrupted oxidant/antioxidants hemostasis of the hepatic tissues. Also, TAA markedly increased the expression of nuclear factor kappa-B (NF-KB); and enhanced Toll like receptor 4 (TLR4) as well as NLPR3 inflammosome production. Moreover, there was an elevation in the hepatic levels of tumor necrosis factor-alpha (TNF-α) and interleukin -1 beta (IL-1ß) besides increased immunoexpression of Bcl-2-associated X protein (Bax) as well as caspase 3. In contrast, treatment with sitagliptin significantly attenuated TAA-induced histopathological, biochemical and immunohistochemical alterations. SIGNIFICANCE: Our results suggest that the hepatoprophylactic impact of sitagliptin might be arbitrated via modulating TLR4 and NK-KB signaling cascade followed by depression of inflammation besides apoptosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , NF-kappa B/imunologia , Fosfato de Sitagliptina/uso terapêutico , Tioacetamida/efeitos adversos , Receptor 4 Toll-Like/imunologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
Nat Commun ; 10(1): 2150, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089130

RESUMO

Peptide-major histocompatibility complex class II (pMHCII)-based nanomedicines displaying tissue-specific autoantigenic epitopes can blunt specific autoimmune conditions by re-programming cognate antigen-experienced CD4+ T-cells into disease-suppressing T-regulatory type 1 (TR1) cells. Here, we show that single pMHCII-based nanomedicines displaying epitopes from mitochondrial, endoplasmic reticulum or cytoplasmic antigens associated with primary biliary cholangitis (PBC) or autoimmune hepatitis (AIH) can broadly blunt PBC, AIH and Primary Sclerosing Cholangitis in various murine models in an organ- rather than disease-specific manner, without suppressing general or local immunity against infection or metastatic tumors. Therapeutic activity is associated with cognate TR1 cell formation and expansion, TR1 cell recruitment to the liver and draining lymph nodes, local B-regulatory cell formation and profound suppression of the pro-inflammatory capacity of liver and liver-proximal myeloid dendritic cells and Kupffer cells. Thus, autoreactivity against liver-enriched autoantigens in liver autoimmunity is not disease-specific and can be harnessed to treat various liver autoimmune diseases broadly.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Antígenos de Histocompatibilidade Classe II/imunologia , Hepatopatias/tratamento farmacológico , Nanopartículas/administração & dosagem , Peptídeos/administração & dosagem , Idoso , Animais , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Linhagem Celular , Modelos Animais de Doenças , Epitopos/imunologia , Feminino , Antígenos de Histocompatibilidade Classe II/química , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Nanomedicina/métodos , Nanopartículas/química , Peptídeos/química , Peptídeos/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
7.
J Agric Food Chem ; 67(22): 6169-6176, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31117553

RESUMO

Dietary choline and its containing foods are biotransformed to trimethylamine (TMA) via gut microbial metabolism. Subsequently, as an intermediate molecule, TMA is quickly transported and oxidized in the liver by hepatic flavin monooxygenases to form trimethylamine oxide (TMAO). TMAO was treated as a waste byproduct from choline metabolism, but recent convincing evidence demonstrated the association between the small molecule TMAO and inflammation-related diseases, including blood vessel inflammation and vascular diseases. The scope of this study is to investigate the preventive effect of nobiletin on TMAO-induced blood vessel inflammation. Our results from Western blot showed that the inhibition of TMAO-induced cardiovascular inflammation was correlated with nobiletin-mediated inhibitory effects on NF-κB and MAPK/ERK related pathways. More specifically, nobiletin prevented the oxidative damage of vascular sites (proximal aorta), inhibited the activity of MAPK/ERK, reduced the expression of NF-κB p65 and phospho-NF-κB p65, and consequently decreased the inflammatory response. Flow cytometry analyses showed that nobiletin decreased TMAO-induced apoptosis of HUVEC cells and counteracted TMAO-induced HUVEC cell proliferation. Results from HE staining and immunohistochemical results also showed that nobiletin reduced the degree of inflammation of the proximal aorta in Sprague-Dawley rats. In summary, nobiletin significantly reduced TMAO-induced vascular inflammation via inhibition of the NF-κB/MAPK pathways.


Assuntos
Flavonas/administração & dosagem , Quinases de Proteína Quinase Ativadas por Mitógeno/imunologia , Fator de Transcrição RelA/imunologia , Doenças Vasculares/prevenção & controle , Animais , Aorta/efeitos dos fármacos , Aorta/imunologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Masculino , Metilaminas/efeitos adversos , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/genética , Doenças Vasculares/induzido quimicamente , Doenças Vasculares/genética , Doenças Vasculares/imunologia
8.
J Food Sci ; 84(6): 1586-1591, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31116885

RESUMO

The objective of this study was to evaluate the effects of a hot-water extract of defatted Camellia oleifera seeds (CSE) in carbon tetrachloride (CCl4 )-induced liver damage in rats. Wistar rats were separated into four groups including the normal (N) and CCl4 control (C) groups, which are fed a control diet, and the CCL (low-dose CSE) and CCH (high-dose CSE) groups, which are fed with a control diet plus different amount of CSE for an 8-week experimental period. Liver injury in the C, CCL, and CCH groups was induced by injecting CCl4 (i.p.) twice a week from the 5th week to the end of the study. In CCl4 -treated rats, the alanine transaminase (ALT) and aspartate transaminase (AST) activities and malondialdehyde (MDA) concentration significantly increased compared to the normal group. Lower antioxidative enzyme activities and higher proinflammatory cytokines, transforming growth factor-ß (TGF-ß) and hydroxyproline concentrations in the liver were also found in the CCl4 -treated group compared to the normal group. In contrast, the administration of CSE alleviated the biochemical and histopathological changes including inflammation, liver cell damage, and fibrosis caused by CCl4 in rats. Our results indicated that CSE exhibited hepatoprotective effects in CCl4 -induced liver hepatotoxicity through alleviating hepatic inflammation and fibrosis in rats. PRACTICAL APPLICATION: Camellia oleifera are widely used for edible oil production while the defatted seeds pomace is often discarded. We found that extract of C. oleifera pomace containing phenolic compounds, saponins, and polysaccharides showed protective effects chemical-driven liver damage and, therefore, may be used in further studies and developing functional foods.


Assuntos
Camellia/química , Hepatopatias/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Alanina Transaminase/imunologia , Animais , Tetracloreto de Carbono/efeitos adversos , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/etiologia , Hepatopatias/imunologia , Masculino , Malondialdeído/imunologia , Ratos , Ratos Wistar
9.
Fish Shellfish Immunol ; 90: 308-316, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059812

RESUMO

Japanese pufferfish (Takifugu rubripes) is one of the main marine aquatic fish species cultured in Asia due to its high nutritional value. In recent years, disease caused by Vibrio harveyi infections have led to serious mortality in Japanese pufferfish industry. To understand the complex molecular mechanisms between V. harveyi and Japanese pufferfish, we performed a transcriptome analysis of liver and spleen samples from Japanese pufferfish at 1 and 2 day post-infection. Between-group comparisons revealed 922 genes that were significantly differentially expressed. The altered genes emphasized the function in several immune related pathways including MAPK signaling pathway, JAK-STAT signaling pathway, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction and lysosomal pathway. The data generated in this study provided insight into the responses of Japanese pufferfish against V. harveyi at the transcriptome level, promoting our comprehensive understanding of immune responses for aquatic animal against V. harveyi.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Takifugu/genética , Takifugu/imunologia , Transcriptoma/imunologia , Vibrio/fisiologia , Animais , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica/veterinária , Fígado/imunologia , Fígado/metabolismo , Distribuição Aleatória , Baço/imunologia , Baço/metabolismo , Takifugu/metabolismo , Vibrioses/imunologia , Vibrioses/veterinária
10.
Cancer Immunol Immunother ; 68(6): 961-971, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30955067

RESUMO

Hepatocellular carcinoma (HCC) is the third most lethal cancer in the world. Natural killer (NK) cell-mediated immunity is crucial for tumor surveillance and therapy. Characterization of the regulatory mechanisms of NK cell function is important for developing novel immunotherapies against HCC. In this study, we used a chemical-induced mouse HCC model to identify the upregulation of Sirtuin2 (SIRT2) in liver NK cells. In particular, SIRT2 was predominantly expressed in liver CD94+ NK cells. The HCC liver microenvironment induced SIRT2 expression in NK cells. In addition, overexpression of exogenous SIRT2 significantly upregulated the production of cytokines and cytotoxic mediators in activated NK cells. Consistently, SIRT2-overexpressing NK cells showed a stronger tumoricidal effect on hepatoma cells. Moreover, SIRT2 remarkably promoted the phosphorylation of Extracellular-signal-regulated kinase 1/2 (Erk1/2) and p38 Mitogen-activated protein kinases (MAPK) in activated NK cells. SIRT2 knockdown in liver CD94+ NK cells impaired their cytotoxic effect on hepatoma cells. Our study indicates that SIRT2 enhances the tumoricidal activity of liver NK cells in HCC.


Assuntos
Carcinoma Hepatocelular/imunologia , Citotoxicidade Imunológica/imunologia , Células Matadoras Naturais/imunologia , Neoplasias Hepáticas Experimentais/imunologia , Fígado/imunologia , Sirtuína 2/imunologia , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Citocinas/imunologia , Citocinas/metabolismo , Citotoxicidade Imunológica/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoterapia Adotiva , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/transplante , Fígado/metabolismo , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/terapia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Interferência de RNA , Sirtuína 2/genética , Sirtuína 2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
Medicine (Baltimore) ; 98(17): e15414, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027143

RESUMO

Alpha-fetoprotein (AFP), as the most widely used biomarker of hepatocellular carcinoma (HCC), was correlated with ongoing liver damage. The aim of this study was to evaluate the ability of inflammatory correction-based AFP to identify HCC from other liver diseases.From March 2012 to March 2017, among 926 participants, a total of 501 patients whose transaminases were higher than the upper limit of normal range, including 166 treatment-naïve HCC patients were enrolled in our retrospective study. The liver function, white blood cell (WBC) count and serum AFP level of all patients were collected at the initial stage of admission. The area under the receiver-operating curve (AUROC) of AFP, AFP/(Aspartate aminotransferase*Alanine aminotransferase) [AFP/(AST*ALT)] and AFP/WBC were compared between the HCC group and the control groups for the quantifying diagnostic efficacy.AUROCs of our novel index AFP/(AST*ALT) were up to 0.853 (95% confidence interval, CI 0.818-0.887, P < .001) and 0.825 (95% CI 0.782-0.868, P < .001), respectively, when differentiating HCC from non-HCC patients and from cirrhosis patients, which was superior to AFP and AFP/WBC. Diagnostic performance of AFP/(AST*ALT) could be verified in hepatitis B virus (HBV)- or hepatitis C virus (HCV)-associated HCC patients as well. What's more, AFP/(AST*ALT) had a significant positive and moderate correlation with tumor diameter and presence of cancerous emboli or not (Spearman correlation coefficients were 0.323 and 0.305, respectively; both P < .001). For predicting HCC, the optimal cut-off value of AFP/(AST*ALT) is 1.603, and the sensitivity and specificity were 82.8% and 72.7%, respectively, which were significantly higher than the AFP and AFP/WBC.The serum AFP levels based on correction of liver inflammation can effectively improve the diagnostic performance of HCC, providing a new indicator that is simple, economical and pervasive for clinic.


Assuntos
Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Transaminases/sangue , alfa-Fetoproteínas/metabolismo , Adulto , Área Sob a Curva , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/imunologia , Feminino , Humanos , Inflamação/sangue , Inflamação/enzimologia , Inflamação/imunologia , Contagem de Leucócitos , Fígado/enzimologia , Fígado/imunologia , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
12.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999584

RESUMO

Innate lymphoid cells (ILCs) represent a heterogeneous population of recently discovered immune cells that mirror the functions of adaptive T lymphocytes. However, ILCs are devoid of specific antigen receptors and cellular activation depends on environmental cytokines, rendering them as early regulators of immune responses. Type 2 innate lymphoid cells (ILC2s) respond to alarmins, such as interleukin-25 and -33 and shape Th2-associated immunity by expressing IL-5 and IL-13 in a GATA3-dependent manner. In addition, ILC2s express the epidermal growth factor-like molecule Amphiregulin thereby promoting regeneration of injured tissue during inflammation. The gut and liver confer nutrient metabolism and bidirectional exchange of products, known as the gut-liver axis. Accordingly, both organs are continuously exposed to a large variety of harmless antigens. This requires avoidance of immunity, which is established by a tolerogenic environment in the gut and liver. However, dysregulations within the one organ are assumed to influence vitality of the other and frequently promote chronic inflammatory settings with poor prognosis. Intensive research within the last years has revealed that ILC2s are involved in acute and chronic inflammatory settings of gut and liver. Here, we highlight the roles of ILC2s in intestinal and hepatic inflammation and discuss a regulatory potential.


Assuntos
Inflamação/imunologia , Intestinos/imunologia , Fígado/imunologia , Ativação Linfocitária , Linfócitos/imunologia , Animais , Movimento Celular , Citocinas/imunologia , Humanos , Imunidade Inata , Intestinos/citologia , Fígado/citologia , Linfócitos/citologia
13.
Biomed Res Int ; 2019: 8319465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019973

RESUMO

The pathogens Schistosoma mansoni and Paracoccidioides brasiliensis share common geographic areas, determining infectious diseases with high mortality rates worldwide. Histopathological and immunological changes induced by each pathogen are well understood; however, the host responses to S. mansoni and P. brasiliensis coinfection are still unknown. Thus, we investigated liver damage and cytokines production in a murine model acutely and chronically coinfected with these pathogens. Fourty male Swiss mice were infected with S. mansoni and P. brasiliensis alone or coinfected. The animals were euthanized with 50 (acute infection) and 120 (chronic infection) days of infection. All infected animals exhibited liver inflammation. Intense granulomatous inflammation was detected in animals infected with S. mansoni alone and those coinfected. Productive and involutive granulomas were clearly observed in acute and chronic infections, respectively. Granuloma size was reduced in the acute phase and increased in the chronic phase of S. mansoni and P. brasiliensis coinfection, compared with animals infected only with S. mansoni. In the chronic phase of infection, the granulomatous inflammation in coinfected animals was characterized by intense neutrophils accumulation and reduced eosinophils number. IFN-γ, IL-2, IL-4, and IL-5 circulating levels were increased in all infected groups. Coinfected animals presented attenuated IFN-γ and IL-4 production in the acute and chronic infections. Taken together, our findings indicate that coinfected animals exhibited a differential modulation of granulomatous inflammation during the acute and chronic phases of infection, which was potentially associated with a divergent profile of cytokines production and migration of neutrophils and eosinophils in response to S. mansoni and P. brasiliensis antigenic stimulation.


Assuntos
Coinfecção , Granuloma , Hepatopatias , Fígado , Paracoccidioides/imunologia , Paracoccidioidomicose , Schistosoma mansoni/imunologia , Esquistossomose mansoni , Animais , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/patologia , Modelos Animais de Doenças , Granuloma/imunologia , Granuloma/microbiologia , Granuloma/parasitologia , Granuloma/patologia , Fígado/imunologia , Fígado/microbiologia , Fígado/parasitologia , Fígado/patologia , Hepatopatias/imunologia , Hepatopatias/microbiologia , Hepatopatias/parasitologia , Hepatopatias/patologia , Masculino , Camundongos , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/patologia , Paracoccidioidomicose/fisiopatologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/microbiologia , Esquistossomose mansoni/patologia
14.
In Vivo ; 33(3): 749-755, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028193

RESUMO

BACKGROUND/AIM: Staphylococcus aureus (S. aureus) is a major gram-positive pathogen, which can cause toxic and immunogenic injuries both in nosocomial and community-acquired infections. Peroxiredoxin (Prx) I plays crucial roles in cellular apoptosis, proliferation, and signal transduction as well as in immunoregulation. The present study aimed to investigate whether Prx I protects mice from death caused by the heat-killed Staphylococcus aureus. MATERIALS AND METHODS: In the present study, we challenged the wild-type and Prx I-deficient mice with heat-killed S. aureus (HKSA). The effects of Prx I were evaluated by a series of in vitro and in vivo experiments including western blot, Haematoxylin and Eosin staining, splenocyte analysis and cytokines analysis. RESULTS: Intra-peritoneal (ip) inoculation of HKSA resulted in increased mortality of Prx I-knockout (KO) mice with severe liver damage and highly populated spleens with lymphocytes. Furthermore, HKSA infections also bursted the production of both pro-inflammatory and anti-inflammatory serum cytokines in Prx I KO compared to wild-type mice. CONCLUSION: Enhanced mortality of S. aureus-infected mice with Prx I deficiency suggested that Prx I may protect against the infection-associated lethality of mice.


Assuntos
Peroxirredoxinas/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Animais , Apoptose , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Mortalidade , Peroxirredoxinas/genética , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/genética
15.
J Immunol Res ; 2019: 2974753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019980

RESUMO

Background and Aim: The presumed role of the inhibitory receptor LAIR-1 (CD305) in the inflammatory response suggests that it might contribute to the pathophysiology of chronic inflammatory diseases such as liver cirrhosis. We studied the LAIR-1 expression on liver macrophages and blood monocytes related to the progression of liver cirrhosis. Methods: The expression of LAIR-1 was analyzed by immunohistochemistry, flow cytometry, and Western blot. Results: We found a decreased number of macrophages expressing LAIR-1 in cirrhotic liver that could be due to a high presence of collagen, ligand of LAIR-1, in the fibrotic tissue which could downregulate its expression or interfere with the immunostaining. The expression of LAIR-1 decreased after cell differentiation, and the total content, but not the cell surface expression, increased after activation in the HL-60 human macrophage in vitro model. Blood monocytes exhibited higher LAIR-1 expression levels in cirrhotic patients, which were evident even in early clinical stages in all monocyte subsets, and greater in the "intermediate" inflammatory monocyte subpopulation. The in vitro activation of human blood monocytes did not increase its expression on the cell surface suggesting that the in vivo increase of LAIR-1 must be the result of a specific combination of stimuli present in cirrhotic patients. This represents an exclusive feature of liver cirrhosis, since blood monocytes from other chronic inflammatory pathologies showed similar or lower LAIR-1 levels compared with those of healthy controls. Conclusions: These results may indicate that monocyte LAIR-1 expression is a new biomarker to early detect liver damage caused by chronic inflammation in liver cirrhosis.


Assuntos
Progressão da Doença , Cirrose Hepática/diagnóstico , Monócitos/imunologia , Receptores Imunológicos/genética , Adulto , Idoso , Biomarcadores/análise , Diferenciação Celular , Feminino , Citometria de Fluxo , Células HL-60 , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Lipopolissacarídeos , Fígado/imunologia , Cirrose Hepática/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade
16.
Anticancer Res ; 39(3): 1191-1196, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842149

RESUMO

BACKGROUND: Despite advances in perioperative management, the 5-year survival rate of patients with esophageal adenocarcinoma (Barrett's cancer) is poor. Adjuvant immunotherapies are currently the subject of clinical trials. The prognostic role of tumor-infiltrating T-lymphocytes (TILs) expressing CD45 has only been investigated in primary tumors. The significance of TILs in the target organs of distant metastases, in particular the liver, is unclear. This study examined the influence of CD45-positive cells in liver parenchyma and primary tumors on cumulative survival. MATERIALS AND METHODS: The density of CD45-positive cells was analyzed immunohistochemically using tissue microarrays. Sixty-five patients for whom a liver biopsy was available in addition to the primary tumor were included in the study. Liver metastases were found in 21 patients. The results of the immunohistochemical analysis were correlated with patient's outcomes. The Cox proportional hazard model was used to compute mortality hazard ratio in consideration of clinical variables. RESULTS: Elevated density of CD45-positive cells in the liver biopsy corresponded with a better cumulative survival rate (p<0.001), while no significant differences were found for primary tumors. Multivariate Cox regression analysis showed that a high density of CD45-positive cells in the liver parenchyma was an independent prognostic parameter of longer overall survival (hazard ratio(HR)=0.432, p=0.048). CONCLUSION: The density of CD45-positive cells in the liver parenchyma is an easily measured prognostic biomarker that can identify patient subgroups with a better prognosis. In addition, the density of CD45-positive cells in the liver may assist as a criterion for selecting patients with a high potential for response to adjuvant immunotherapy.


Assuntos
Adenocarcinoma/imunologia , Neoplasias Esofágicas/imunologia , Antígenos Comuns de Leucócito/imunologia , Neoplasias Hepáticas/imunologia , Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Fígado/imunologia , Fígado/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais
17.
Nat Commun ; 10(1): 1076, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30842418

RESUMO

Phagocytes, including neutrophils and macrophages, have been suggested to function in a cooperative way in the initial phase of inflammatory responses, but their interaction and integration in the resolution of inflammation and tissue repair remain unclear. Here we show that neutrophils have crucial functions in liver repair by promoting the phenotypic conversion of pro-inflammatory Ly6ChiCX3CR1lo monocytes/macrophages to pro-resolving Ly6CloCX3CR1hi macrophages. Intriguingly, reactive oxygen species (ROS), expressed predominantly by neutrophils, are important mediators that trigger this phenotypic conversion to promote liver repair. Moreover, this conversion is prevented by the depletion of neutrophils via anti-Ly6G antibody, genetic deficiency of granulocyte colony-stimulating factor, or genetic deficiency of NADPH oxidase 2 (Nox2). By contrast, adoptive transfer of WT rather than Nox2-/- neutrophils rescues the impaired phenotypic conversion of macrophages in neutrophil-depleted mice. Our findings thus identify an intricate cooperation between neutrophils and macrophages that orchestrate resolution of inflammation and tissue repair.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/imunologia , Regeneração Hepática/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Espécies Reativas de Oxigênio/metabolismo , Acetaminofen/toxicidade , Transferência Adotiva/métodos , Animais , Transplante de Medula Óssea , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Humanos , Fígado/imunologia , Fígado/patologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , NADPH Oxidase 2/genética , NADPH Oxidase 2/imunologia , Neutrófilos/metabolismo , Neutrófilos/transplante , Cultura Primária de Células , Quimeras de Transplante
18.
Food Chem Toxicol ; 126: 277-284, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826410

RESUMO

Alcoholic liver disease (ALD), as one of the most common diseases, has become a global threat to human health. The aim of this study was designed to investigate the hepatoprotective effects of ginsenoside Rk3 against ALD and to discover the potential mechanisms of these protective effects. Mice were intragastrically administered 50% alcohol and treated with ginsenoside Rk3 (25 and 50 mg/kg) once per day for 6 weeks. The results indicated that ginsenoside Rk3 promoted hepatic function through significant downgrading AST and ALT levels in the serum, attenuating oxidative stress, and restoring antioxidant balance in hepatic tissue. Additionally, ginsenoside Rk3 significantly reduced the expression of inflammatory cytokines, such as NF-κB, TNF-α, IL-6, and IL-1ß in the mice. Furthermore, ginsenoside Rk3 supplementation significantly inhibited apoptotic protein expression in the liver. The present study clearly demonstrates that ginsenoside Rk3 exerts a protective effect against ALD-induced liver injury because of its antioxidant, anti-apoptotic, and anti-inflammatory activities. The findings from the present investigation show that ginsenoside Rk3 might be a promising candidate treatment agent against ALD.


Assuntos
Apoptose/efeitos dos fármacos , Etanol/efeitos adversos , Ginsenosídeos/administração & dosagem , Hepatopatias Alcoólicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Animais , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
19.
Nat Commun ; 10(1): 952, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30862827

RESUMO

Tools for noninvasively modulating neural signaling in peripheral organs will advance the study of nerves and their effect on homeostasis and disease. Herein, we demonstrate a noninvasive method to modulate specific signaling pathways within organs using ultrasound (U/S). U/S is first applied to spleen to modulate the cholinergic anti-inflammatory pathway (CAP), and US stimulation is shown to reduce cytokine response to endotoxin to the same levels as implant-based vagus nerve stimulation (VNS). Next, hepatic U/S stimulation is shown to modulate pathways that regulate blood glucose and is as effective as VNS in suppressing the hyperglycemic effect of endotoxin exposure. This response to hepatic U/S is only found when targeting specific sub-organ locations known to contain glucose sensory neurons, and both molecular (i.e. neurotransmitter concentration and cFOS expression) and neuroimaging results indicate US induced signaling to metabolism-related hypothalamic sub-nuclei. These data demonstrate that U/S stimulation within organs provides a new method for site-selective neuromodulation to regulate specific physiological functions.


Assuntos
Vias Neurais/fisiologia , Neuroimunomodulação/fisiologia , Terapia por Ultrassom/métodos , Animais , Fígado/imunologia , Fígado/inervação , Fígado/fisiologia , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Vias Neurais/imunologia , Especificidade de Órgãos , Ratos , Ratos Sprague-Dawley , Baço/imunologia , Baço/inervação , Baço/fisiologia , Estimulação do Nervo Vago
20.
Gut ; 68(8): 1477-1492, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30872395

RESUMO

OBJECTIVE: There is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut-liver crosstalk for CLD in the murine Mdr2 knockout (Mdr2-/-) model resembling human primary sclerosing cholangitis (PSC). DESIGN: Male Mdr2 -/-, Mdr2-/- crossed with hepatocyte-specific deletion of caspase-8 (Mdr2-/- /Casp8∆hepa) and wild-type (WT) control mice were housed for 8 or 52 weeks, respectively, to characterise the impact of Mdr2 deletion on liver and gut including bile acid and microbiota profiling. To block caspase activation, a pan-caspase inhibitor (IDN-7314) was administered. Finally, the functional role of Mdr2-/- -associated intestinal dysbiosis was studied by microbiota transfer experiments. RESULTS: Mdr2-/- mice displayed an unfavourable intestinal microbiota signature and pronounced NLRP3 inflammasome activation within the gut-liver axis. Intestinal dysbiosis in Mdr2-/- mice prompted intestinal barrier dysfunction and increased bacterial translocation amplifying the hepatic NLRP3-mediated innate immune response. Transfer of Mdr2-/- microbiota into healthy WT control mice induced significant liver injury in recipient mice, highlighting the causal role of intestinal dysbiosis for disease progression. Strikingly, IDN-7314 dampened inflammasome activation, ameliorated liver injury, reversed serum bile acid profile and cholestasis-associated microbiota signature. CONCLUSIONS: MDR2-associated cholestasis triggers intestinal dysbiosis. In turn, translocation of endotoxin into the portal vein and subsequent NLRP3 inflammasome activation contribute to higher liver injury. This process does not essentially depend on caspase-8 in hepatocytes, but can be blocked by IDN-7314.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Ductos Biliares , Caspase 8/genética , Inibidores de Caspase/farmacologia , Colangite Esclerosante/metabolismo , Progressão da Doença , Disbiose , Microbioma Gastrointestinal/fisiologia , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Fígado/imunologia , Camundongos , Camundongos Knockout
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA