RESUMEN
Liver fibrosis is a progression of chronic liver disease characterized by excess deposition of fibrillary collagen. The aim of this study was to investigate the protective effect of a triterpenoid-enriched extract (TEE) from bitter melon leaves against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. Male ICR mice received TEE (100 or 150 mg kg-1) by daily oral gavage for one week before starting CCl4 administration and throughout the entire experimental period. After intraperitoneal injection of CCl4 for nine weeks, serum and liver tissues of the mice were collected for biochemical, histopathological and molecular analyses. Our results showed that TEE supplementation reduced CCl4-induced serum aspartate aminotransferase and alanine aminotransferase activities. Histopathological examinations revealed that CCl4 administration results in hepatic fibrosis, while TEE supplementation significantly suppressed hepatic necroinflammation and collagen deposition. In addition, TEE supplementation decreased α-smooth muscle actin (α-SMA)-positive staining and protein levels of α-SMA and transforming growth factor-ß1. TEE-supplemented mice had lower mRNA expression levels of interleukin-6, tumor necrosis factor-α, and toll-like receptor 4. Moreover, TEE (150 mg kg-1) supplementation significantly reduced intrahepatic inflammatory Ly6C+ monocyte infiltration. We demonstrated that TEE could ameliorate hepatic fibrosis by regulating inflammatory cytokine secretion and α-SMA expression in the liver to reduce collagen accumulation.
Asunto(s)
Antiinflamatorios/administración & dosificación , Cirrosis Hepática/tratamiento farmacológico , Momordica charantia/química , Extractos Vegetales/administración & dosificación , Triterpenos/administración & dosificación , Alanina Transaminasa/genética , Alanina Transaminasa/inmunología , Animales , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/inmunología , Tetracloruro de Carbono/efectos adversos , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/inmunología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Hojas de la Planta/química , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Hepatic ischemia-reperfusion (I/R) injury is a complex pathophysiological process that often times occurs in liver transplantation, hepatectomy, and ischemic shock. Aberrant activation of inflammatory responses has been implicated in hepatic I/R injury. In this study, we aimed to investigate the role of circadian clock gene Rev-erbα (a well-known regulator of inflammation) in hepatic I/R injury. We first showed that Rev-erbα ablation sensitized mice to hepatic I/R injury as evidenced by higher levels of plasma alanine aminotransferase and aspartate aminotransferase, an increased histological score, as well as enhanced hepatic myeloperoxidase activity in Rev-erbα-/- mice. More severe hepatic I/R injury in Rev-erbα-/- mice was accompanied by higher expression of pro-inflammatory cytokines, exacerbated activation of Nlrp3 inflammasome, and more extensive infiltration of inflammatory cells. Moreover, pharmacological activation of Rev-erbα by SR9009 significantly alleviated the hepatic damage and inflammatory responses. In addition, I/R operation started at ZT18 (corresponding to low Rev-erbα expression) caused more severe liver damage and inflammatory responses in wild-type mice as compared to operation started at ZT6 (corresponding to high Rev-erbα expression), supporting a protective effect of Rev-erbα on hepatic I/R injury. Collectively, Rev-erbα protects hepatic I/R injury probably via repression of inflammatory responses, and targeting Rev-erbα may be a promising approach for management of hepatic I/R injury.
Asunto(s)
Relojes Circadianos/inmunología , Hígado/metabolismo , Macrófagos/inmunología , Neutrófilos/inmunología , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Daño por Reperfusión/metabolismo , Alanina Transaminasa/genética , Alanina Transaminasa/inmunología , Animales , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/inmunología , Relojes Circadianos/efectos de los fármacos , Relojes Circadianos/genética , Inflamasomas/efectos de los fármacos , Inflamasomas/inmunología , Inflamasomas/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Hígado/inmunología , Hígado/patología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/metabolismo , Linfocitos/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Neutrófilos/patología , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/deficiencia , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/inmunología , Peroxidasa/genética , Peroxidasa/inmunología , Pirrolidinas/farmacología , Daño por Reperfusión/inmunología , Daño por Reperfusión/patología , Tiofenos/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Macrophage-mediated inflammation is a key pathophysiological component of cardiovascular diseases, but the underlying mechanisms by which the macrophage regulates inflammation have been unclear. In our study, we, for the first time, showed an endogenous sulfur dioxide (SO2) production in RAW267.4 macrophages by using HPLC and SO2-specific fluorescent probe assays. Moreover, the endogenous SO2 generating enzyme aspartate aminotransferase (AAT) was found to be expressed by the macrophages. Furthermore, we showed that AAT2 knockdown triggered spontaneous macrophage-mediated inflammation, as represented by the increased TNF-α and IL-6 levels and the enhanced macrophage chemotaxis; these effects could be reversed by the treatment with a SO2 donor. Mechanistically, AAT2 knockdown activated the NF-κB signaling pathway in macrophages, while SO2 successfully rescued NF-κB activation. In contrast, forced AAT2 expression reversed AngII-induced NF-κB activation and subsequent macrophage inflammation. Moreover, treatment with a SO2 donor also alleviated macrophage infiltration in AngII-treated mouse hearts. Collectively, our data suggest that macrophage-derived SO2 is an important regulator of macrophage activation and it acts as an endogenous "on-off switch" in the control of macrophage activation. This knowledge might enable a new therapeutic strategy for cardiovascular diseases.
Asunto(s)
Aspartato Aminotransferasas/genética , Miocitos Cardíacos/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , FN-kappa B/genética , Dióxido de Azufre/farmacología , Angiotensina II/farmacología , Animales , Aspartato Aminotransferasas/antagonistas & inhibidores , Aspartato Aminotransferasas/inmunología , Línea Celular , Quimiotaxis/efectos de los fármacos , Regulación de la Expresión Génica , Inflamación , Interleucina-6/genética , Interleucina-6/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/citología , Miocitos Cardíacos/inmunología , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/inmunología , FN-kappa B/inmunología , Células RAW 264.7 , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Transducción de Señal , Sulfitos/química , Sulfitos/farmacología , Dióxido de Azufre/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Previous studies demonstrate that the number of induced regulatory T cells (iTregs) increases in aged mice. However, these studies do not characterize iTregs across different ages or how these immune modulators contribute to the dysregulation of immunity in murine disease models. Therefore, this study aimed to examine the relationship between age and iTreg function using a mouse model of hepatic ischemia-reperfusion injury (IRI). In this model, aged-mice suffered more serious injury than Young-mice, with higher serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and higher histological scores from liver biopsies. iTregs isolated from Young-mice exhibited stronger immunosuppressive ability in vitro and had a greater response during IRI in vivo. In addition, aged-mice that were pretreated with iTregs generated in Young-mice (Y-iTregs) had alleviated injury compared with mice pretreated with iTregs from aged-mice (A-iTregs) or no treatment group. Adoptive transfer of iTregs ameliorated liver IRI and promoted liver recovery with decreased levels of interferon-γ (IFN-γ) and interleukin-17 (IL-17). These results demonstrate that the exacerbated IRI observed in aged-mice is a result of decreased iTreg function. Therefore, improving iTreg function is important for disease treatment in elder patients.
Asunto(s)
Envejecimiento/inmunología , Hígado/inmunología , Daño por Reperfusión/inmunología , Linfocitos T Reguladores/inmunología , Traslado Adoptivo , Factores de Edad , Alanina Transaminasa/sangre , Alanina Transaminasa/inmunología , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/inmunología , Aspartato Aminotransferasas/metabolismo , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-17/inmunología , Interleucina-17/metabolismo , Hígado/patología , Hígado/fisiopatología , Ratones Endogámicos C57BL , Daño por Reperfusión/fisiopatología , Daño por Reperfusión/terapia , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/trasplanteRESUMEN
The aim of the present study was to investigate the effect of chitosan (a naturally derived polymer) on the immune responses and glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) levels in WEHI3 cellgenerated leukemia mice. Mice were divided into control, WEHI3 control, acetic acid (vehicle)treated, and 5 and 20 mg/kg chitosantreated groups. Mice were subsequently weighed, blood was collected, and liver and spleen samples were isolated and weighed. Blood samples were measured for cell markers, the spleen underwent phagocytosis and natural killer (NK) cell activity examination, and cell proliferation was analyzed by flow cytometry. Chitosan did not significantly affect the weights of body, liver and spleen at 5 and 20 mg/kg treatment. Chitosan increased the percentage of CD3 (T cells marker), decreased the levels of CD19 (Bcell marker) and CD11b at 5 mg/kg treatment, and decreased the levels of Mac3 at 5 and 20 mg/kg treatment. Chitosan significantly increased macrophage phagocytosis of PBMCs, but did not significantly affect macrophage phagocytosis in the peritoneal cavity. Chitosan treatment did not significantly affect the cytotoxic activity of NK cells, and also did not affect T- and B-cell proliferation. Chitosan significantly increased total white blood cell numbers, and GOT and GPT activities were both significantly increased. However, chitosan did not significantly affect LDH activity in leukemia mice. Chitosan may aid in future studies on improving immune responses in the treatment of leukemia.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Quitosano/uso terapéutico , Inmunidad Celular/efectos de los fármacos , L-Lactato Deshidrogenasa/sangre , Leucemia/tratamiento farmacológico , Adyuvantes Inmunológicos/farmacología , Alanina Transaminasa/inmunología , Animales , Aspartato Aminotransferasas/inmunología , Línea Celular Tumoral , Quitosano/farmacología , Citotoxicidad Inmunológica/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , L-Lactato Deshidrogenasa/inmunología , Leucemia/sangre , Leucemia/inmunología , Recuento de Leucocitos , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Fagocitosis/efectos de los fármacosRESUMEN
Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1+ cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1+ cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1+ cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1+ cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut.
Asunto(s)
Antígenos Ly/inmunología , Células Asesinas Naturales/inmunología , Subfamilia B de Receptores Similares a Lectina de Células NK/inmunología , Choque Hemorrágico/inmunología , Heridas y Lesiones/inmunología , Alanina Transaminasa/sangre , Alanina Transaminasa/inmunología , Animales , Antígenos Ly/sangre , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/inmunología , Citocinas/sangre , Citocinas/inmunología , Células Asesinas Naturales/metabolismo , Ratones , Subfamilia B de Receptores Similares a Lectina de Células NK/sangre , Choque Hemorrágico/sangre , Choque Hemorrágico/patología , Heridas y Lesiones/sangre , Heridas y Lesiones/patologíaRESUMEN
The massive meat production of broiler chickens make them continuously exposed to potential stressors that stimulate releasing of stress-related hormones like corticosterone (CORT) which is responsible for specific pathways in biological mechanisms and physiological activities. Therefore, this research was conducted to evaluate a wide range of responses related to broiler performance, immune function, plasma biochemistry, related gene expressions and cell death morphology during and after a 7-day course of CORT injection. A total number of 200 one-day-old commercial Cobb broiler chicks were used in this study. From 21 to 28 d of age, broilers were randomly assigned to one of 2 groups with 5 replicates of 20 birds each; the first group received a daily intramuscular injection of 5 mg/kg BW corticosterone dissolved in 0.5 ml ethanol:saline solution (CORT group), while the second group received a daily intramuscular injection of 0.5 ml ethanol:saline only (CONT group). Growth performance, including body weight (BW), daily weight gain (DG), feed intake (FI) and feed conversion ratio (FC), were calculated at 0, 3 and 7 d after the start of the CORT injections. At the same times, blood samples were collected in each group for hematological (TWBC's and H/L ratio), T- and B-lymphocytes proliferation and plasma biochemical assays (total protein, TP; free triiodothyronine hormone, fT3; aspartate amino transaminase, AST; and alanine amino transaminase, ALT). The liver, thymus, bursa of Fabricius and spleen were dissected and weighed, and the mRNA expression of insulin-like growth factor 1 gene (IGF-1) in liver and cell-death-program gene (caspase-9) in bursa were analyzed for each group and time; while the apoptotic/necrotic cells were morphologically detected in the spleen. From 28 to 35 d of age, broilers were kept for recovery period without CORT injection and the same sampling and parameters were repeated at the end (at 14 d after initiation of the CORT injection). In general, all parameters of broiler performance were negatively affected by the CORT injection. In addition, CORT treatment decreased the plasma concentration of fT3 and the mRNA expression of hepatic IGF-1. A significant increase in liver weight accompanied by an increase in plasma TP, AST and ALT was observed with CORT treatment, indicating an incidence of liver malfunction by CORT. Moreover, the relative weights of thymus, bursa and spleen decreased by the CORT treatment with low counts of TWBC's and low stimulation of T & B cells while the H/L ratio increased; indicating immunosuppressive effect for CORT treatment. Furthermore, high expression of caspase-9 gene occurred in the bursa of CORT-treated chickens, however, it was associated with a high necrotic vs. low apoptotic cell death pathway in the spleen. Seven days after termination of the CORT treatment in broilers, most of these aspects remained negatively affected by CORT and did not recover to its normal status. The current study provides a comprehensive view of different physiological modulations in broiler chickens by CORT treatment and may set the potential means to mount a successful defense against stress in broilers and other animals as well.
Asunto(s)
Proteínas Aviares/inmunología , Pollos/inmunología , Corticosterona/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Carne , Alanina Transaminasa/genética , Alanina Transaminasa/inmunología , Crianza de Animales Domésticos , Animales , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/inmunología , Proteínas Aviares/genética , Linfocitos B/citología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Bolsa de Fabricio/efectos de los fármacos , Bolsa de Fabricio/inmunología , Caspasa 9/genética , Caspasa 9/inmunología , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Pollos/crecimiento & desarrollo , Ingestión de Alimentos/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos , Inyecciones Intramusculares , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/inmunología , Hígado/efectos de los fármacos , Hígado/inmunología , Bazo/efectos de los fármacos , Bazo/inmunología , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Timo/efectos de los fármacos , Timo/inmunología , Triyodotironina/genética , Triyodotironina/inmunología , Aumento de Peso/efectos de los fármacosRESUMEN
To investigate the impact of epoetin beta (EPO) on sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients treated with peginterferon-ribavirin (RBV). Controlled, randomized, pragmatic multicenter study to assess 2 strategies, ie, the use (EPO group) or nonuse (control group) of EPO in terms of achieving SVR in treatment-naive, genotype non-2/non-3 HCV-infected patients receiving a 48-week treatment regimen of pegylated interferon α-2a (peg-IFN) plus RBV (randomization 2:1). The single-nucleotide polymorphisms of interferon lambda 3 (IFNL3) (rs12979860 and rs8099917), interferon lambda 4 (IFNL4) (ss469415590), and inosine triphosphatase (ITPA) (rs1127354 and rs7270101) were determined retrospectively. Two hundred twenty-seven patients were included in the study. In the global population (n = 227), the overall SVR rate was 52% (118/227). Nonresponse and relapse occurred in respectively 46/227 (20.3%) and 42/227 (18.5%) patients. In the intention-to-treat analysis, 55.5% of patients with anemia (n = 164) had a SVR, specifically 57.4% in the EPO group versus 52.4% in the control group, but the difference was not statistically significant. In the anemic population, independent factors associated with SVR were IFNL3 and IFNL4 polymorphisms, pretreatment HCV RNA level, iron level, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio. EPO has little impact on SVR in patients treated with peg-IFN+RBV and should be recommended only for patients with severe anemia.
Asunto(s)
Anemia/tratamiento farmacológico , Antivirales/uso terapéutico , Eritropoyetina/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , ARN Viral/antagonistas & inhibidores , Ribavirina/uso terapéutico , Adulto , Alanina Transaminasa/genética , Alanina Transaminasa/inmunología , Anemia/sangre , Anemia/complicaciones , Anemia/virología , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/inmunología , Quimioterapia Combinada , Femenino , Expresión Génica , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Interferones , Interleucinas/genética , Interleucinas/inmunología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pirofosfatasas/genética , Pirofosfatasas/inmunología , ARN Viral/biosíntesis , Proteínas Recombinantes/uso terapéutico , Recurrencia , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the role of CD38 in lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute hepatic injury in mice and explore the potential mechanism. METHODS: A mouse model of acute hepatic injury was induced by an intraperitoneal injection (i.p.) of D-GalN and LPS. C57BL/6 wild-type mice (WT) and CD38 gene knockout mice (CD38 KO) were randomly divided into normal control group, early model group (2 hours after i.p. of LPS/D-GalN) and late model group (6 hours after i.p. of LPS/D-GalN), respectively. Two and six hours after administration of D-GalN/LPS, WT mice and CD38 KO mice were sacrificed, and the blood and liver tissue were collected. Serum was used to detect the alanine aminotransferases (ALT) and glutamate oxaloacetate transaminase (AST) levels. The injury of liver was assessed by HE staining. The expressions of IL-1ß, IL-6, TNF-α and IFN-γ were analyzed by real-time quantitative PCR. RESULTS: Compared with the WT mice, CD38 KO mice presented significant increases of serum ALT and AST, mRNA expressions of IL-1ß, IL-6, TNF-α and IFN-γ, as well as hepatocellular necrosis and bleeding in liver tissues after LPS/D-GalN induction. CONCLUSION: CD38 protein effectively reduces the LPS/D-GalN-induced damage of liver tissues via depressing the expressions of inflammatory cytokines and inhibiting the death of liver cells.
Asunto(s)
ADP-Ribosil Ciclasa 1/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Citocinas/inmunología , Regulación hacia Abajo/inmunología , ADP-Ribosil Ciclasa 1/deficiencia , ADP-Ribosil Ciclasa 1/genética , Enfermedad Aguda , Alanina Transaminasa/sangre , Alanina Transaminasa/inmunología , Animales , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Citocinas/genética , Modelos Animales de Enfermedad , Galactosamina , Expresión Génica/inmunología , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Inyecciones Intraperitoneales , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Lipopolisacáridos , Ratones Endogámicos C57BL , Ratones Noqueados , Distribución Aleatoria , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVES: To measure the levels of serum soluble death receptor 5 (sDR5) in patients with hepatitis B. DESIGN AND METHODS: sDR5 concentration in 60 HBV infected patients and 30 healthy volunteers were measured by ELISA. RESULTS: sDR5 concentration in the HBV infected patients was decreased and correlated with serum ALT, Tbil level, albumin/globulin ratio and HBV antigen level. CONCLUSIONS: Decreased serum sDR5 is associated with high level of liver damage and inhibited HBV antigen expression.
Asunto(s)
Antígenos Virales/inmunología , Hepatitis B Crónica/inmunología , Hígado/inmunología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/inmunología , Alanina Transaminasa/sangre , Alanina Transaminasa/inmunología , Antígenos Virales/sangre , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/inmunología , Bilirrubina/sangre , Bilirrubina/inmunología , Ensayo de Inmunoadsorción Enzimática , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/virología , Interacciones Huésped-Patógeno/inmunología , Humanos , Hígado/patología , Hígado/virología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/sangre , SolubilidadAsunto(s)
Aspartato Aminotransferasas/sangre , Inmunoglobulina G/metabolismo , Intercambio Materno-Fetal/inmunología , Complicaciones del Embarazo/inmunología , Aspartato Aminotransferasas/inmunología , Sitios de Unión , Cromatografía Líquida de Alta Presión , Femenino , Sangre Fetal/metabolismo , Estudios de Seguimiento , Humanos , Inmunoglobulina G/inmunología , Inmunoprecipitación , Masculino , Linaje , Embarazo , Remisión Espontánea , Factores de TiempoRESUMEN
Endogenous interleukin-6 has been considered as an important anti-inflammatory cytokine controlling both local and systemic acute inflammatory responses; the usefulness of IL-6 in endotoxemia aiming to block the production of reactive oxygen species and the release of inflammatory cytokines is under discussion The aim of the study was to evaluate the protective effects of IL-6 in experimentally induced endotoxemia in mice correlating the changes in tissue anti-oxidant enzymes and circulating cytokines. Liver injury in low-dose bacterial lipopolysaccharide (5 microg/mouse)-induced endotoxemic mice receiving IL-6 (300 ng/mouse) treatment either before or after LPS injection was detected by the estimation of serum oxaloacetate transaminase and serum glutamate pyruvate transaminase. This finding supports that liver injury during experimental endotoxemia could be lowered by IL-6. Current data also demonstrate the critical role of IL-6 in inducing SOD in liver, whereas IL-6 prior and after LPS challenge group showed reduced PMN infiltration in the liver as evident by decreased hepatic MPO content in those mice. IL-6 treatment also showed higher IL-10 production in serum than endotoxic group as IL-10 is a potent and pleiotropic anti-inflammatory cytokine that inhibits the synthesis of pro-inflammatory cytokines and also has a suppressive effect on pro-inflammatory cytokine like TNF-alpha, IFN-gamma and IL-12. It is also directly involved in the modulation of other aspects of inflammation, particularly cytokine responses and inflammatory cell infiltration.
Asunto(s)
Antioxidantes/metabolismo , Endotoxemia/prevención & control , Interleucina-6/farmacología , Lipopolisacáridos/toxicidad , Hígado/enzimología , Peroxidasa/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/inmunología , Endotoxemia/enzimología , Endotoxemia/inmunología , Endotoxemia/patología , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-12/sangre , Hígado/inmunología , Hígado/patología , Masculino , Ratones , Neutrófilos/inmunología , Neutrófilos/metabolismo , Neutrófilos/patología , Peroxidasa/inmunología , Superóxido Dismutasa/inmunología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
The aims of this study were to observe the relationship between injury of graft and expression of redox factor-1 (Ref-1) in early period (24 h) after liver transplantation in rat model. One hundred and fifty adult male Wister rats were randomly divided into three groups including liver transplant group, sham surgery group and untreated control group. After liver transplantation, animals were sacrificed at different time points, and the changes and significance of the expression of Ref-1 were then explored by immunohistochemistry, serology and histopathology. As compared with sham surgery group and untreated control group, the expression of Ref-1 protein in transplant group was stronger in early period after liver transplantation. With pathology analysis, lots of infiltrating inflammation cells were found around the portal veins. Hepatic tissues were injury. However, the injury in sham surgery and untreated control group were comparatively slight. The serum ALT and AST levels reached the peak at 6-12 h, and decreased significantly after 12 h. These data suggested that the degree of liver injury in earlier period after transplantation peaked at 6 h and then decreased. And Ref-1 protein induced by hepatic ischemic reperfusion injury might play a critical role in repairing the injury.
Asunto(s)
Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Hígado/metabolismo , Daño por Reperfusión/inmunología , Alanina Transaminasa/genética , Alanina Transaminasa/inmunología , Animales , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/inmunología , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/inmunología , Inmunohistoquímica , Inflamación , Hígado/inmunología , Hígado/patología , Trasplante de Hígado , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismoAsunto(s)
Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/inmunología , Inmunoglobulinas/sangre , Hepatopatías/diagnóstico , Anciano , Alanina Transaminasa/sangre , Consumo de Bebidas Alcohólicas , Disnea/diagnóstico , Femenino , Humanos , Inmunoglobulinas/inmunología , Pruebas de Función HepáticaRESUMEN
Bacterial LPS (endotoxin) is implicated in the pathogenesis of acute liver failure and several chronic inflammatory liver diseases. To evaluate the effect of hepatocyte cyclooxygenase (COX)-2 in LPS-induced liver injury, we generated transgenic mice with targeted expression of COX-2 in the liver by using the albumin promoter-enhancer driven vector and the animals produced were subjected to a standard experimental protocol of LPS-induced acute fulminant hepatic failure (i.p. injection of low dose of LPS in combination with d-galactosamine (d-GalN)). The COX-2 transgenic mice exhibited earlier mortality, higher serum aspartate aminotransferase and alanine aminotransferase levels and more prominent liver tissue damage (parenchymal hemorrhage, neutrophilic inflammation, hepatocyte apoptosis, and necrosis) than wild-type mice. Western blot analysis of the liver tissues showed that LPS/d-GalN treatment for 4 h induced much higher cleavage of poly(ADP-ribose) polymerase, caspase-3, and caspase-9 in COX-2 transgenic mice than in wild-type mice. Increased hepatic expression of JNK-2 in COX-2 transgenic mice suggest that up-regulation of JNK-2 may represent a potential mechanism for COX-2-mediated exacerbation of liver injury. Blocking the prostaglandin receptor, EP(1), prevented LPS/d-GalN-induced liver injury and hepatocyte apoptosis in COX-2 transgenic mice. Accordingly, the mice with genetic ablation of EP(1) showed less LPS/d-GalN-induced liver damage and less hepatocyte apoptosis with prolonged survival when compared with the wild-type mice. These findings demonstrate that COX-2 and its downstream prostaglandin receptor EP(1) signaling pathway accelerates LPS-induced liver injury. Therefore, blocking COX-2-EP(1) pathway may represent a potential approach for amelioration of LPS-induced liver injury.
Asunto(s)
Ciclooxigenasa 2/inmunología , Hepatocitos/inmunología , Lipopolisacáridos/toxicidad , Fallo Hepático Agudo/inmunología , Transducción de Señal/inmunología , Alanina Transaminasa/sangre , Alanina Transaminasa/genética , Alanina Transaminasa/inmunología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/inmunología , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/inmunología , Caspasa 3/genética , Caspasa 3/inmunología , Caspasa 3/metabolismo , Caspasa 9/genética , Caspasa 9/inmunología , Caspasa 9/metabolismo , Enfermedad Crónica , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Galactosamina/toxicidad , Expresión Génica , Hemorragia/enzimología , Hemorragia/genética , Hemorragia/inmunología , Hemorragia/patología , Hepatitis/genética , Hepatitis/inmunología , Hepatitis/metabolismo , Hepatitis/patología , Hepatocitos/enzimología , Hepatocitos/patología , Humanos , Fallo Hepático Agudo/enzimología , Fallo Hepático Agudo/genética , Fallo Hepático Agudo/patología , Ratones , Ratones Transgénicos , Proteína Quinasa 9 Activada por Mitógenos/genética , Proteína Quinasa 9 Activada por Mitógenos/inmunología , Proteína Quinasa 9 Activada por Mitógenos/metabolismo , Necrosis/enzimología , Necrosis/genética , Necrosis/inmunología , Necrosis/patología , Especificidad de Órganos/efectos de los fármacos , Especificidad de Órganos/genética , Especificidad de Órganos/inmunología , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/inmunología , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
The immunosuppressive effects of bath exposure to a sub lethal concentration of the synthetic pyrethroid alpha-permethrin (3.05 x 10(-4) mg l(-1)) in the Indian Major carp, Labeo rohita was studied after 45 days' exposure. In some groups, the effects of alpha-permethrin on non-specific defences and serum enzymes of carp were investigated after challenge with Aeromonas hydrophila. Several nonspecific immune responses and serum enzymes were reduced after exposure of alpha-permethrin. Bactericidal activity of rohu serum was reduced significantly in pesticide and bacteria treated fish. The Glutamic Oxaloacetate Transaminase (GOT) and Glutamic Pyruvate Transaminase (GPT) activity were increased in immunosuppressed fish. Blood glucose level was elevated significantly and Hb% was reduced significantly in pesticide and bacteria treated fishes as compared to the negative control.
Asunto(s)
Carpas/inmunología , Inmunidad Innata/efectos de los fármacos , Inmunosupresores/toxicidad , Permetrina/toxicidad , Aeromonas hydrophila/inmunología , Alanina Transaminasa/inmunología , Análisis de Varianza , Animales , Acuicultura/métodos , Aspartato Aminotransferasas/inmunología , Glucemia/inmunología , IndiaRESUMEN
We describe a case of chronic elevation of serum aspartate aminotransferase (AST) activity due to the presence of a macro-enzyme form of AST (macro-AST) in a young female followed up for 12 years. This biochemical abnormality, although generally detected in acute and chronic hepatitis, malignancies and autoimmune disease, was not associated with any particular illness and did not seem to be congenital, as normal AST concentrations were reported in the patient's family members. Moreover, the normal or quasi-normal values of AST associated with peak levels observed in our case suggest that this phenomenon has a fluctuating behaviour rather than persisting for many months or years. In conclusion, we believe that it is important: 1) to reassure the patient with macro-AST, as this condition has a benign evolution and does not require any specific treatment; 2) to keep in mind this biochemical abnormality in all cases of unexplained AST elevation in order to avoid unnecessary invasive diagnostic procedures.
Asunto(s)
Aspartato Aminotransferasas/sangre , Adulto , Alanina Transaminasa/sangre , Complejo Antígeno-Anticuerpo/sangre , Aspartato Aminotransferasas/inmunología , Femenino , Estudios de Seguimiento , Humanos , PronósticoRESUMEN
Wolbachia are intracellular alpha-proteobacteria, closely related to Rickettsia, that infect various arthropods and filarial parasites. In the present study, the cDNA encoding the aspartate aminotransferase (AspAT) of Wolbachia from the human pathogenic filarial parasite Onchocerca volvulus (Ov-WolAspAT) was identified. At the amino acid level, the identity of the Ov-WolAspAT was 56% to Rickettsia prowazekii AspAT and 54% to the AspAT of the nitrogen-fixing bacterium Sinorhizobium meliloti, but the highest degree of identity was found to the putative AspAT of Wolbachia from Brugia malayi and Drosophila melanogaster (85%). All of these bacterial AspATs are members of the AspAT subclass Ib. A 35 kDa fragment of the Ov-WolAspAT was expressed in Escherichia coli, and immunolocalization using polyclonal antibodies against this antigen revealed that Ov-WolAspAT is present in a considerable proportion of the Wolbachia from O. volvulus, as well as in the endobacteria of several other filarial parasites. Western blot analysis using recombinant Ov-WolAspAT as antigen showed that IgG1 antibodies were present in 70 (51%) individuals living in areas endemic for O. volvulus, B. malayi or Wuchereria bancrofti and no IgG4 or IgE antibodies were found. Among 40 sera of persons from Uganda and Liberia who were putatively not infected with human filarial parasites, 11 (28%) individuals presented IgG1 antibodies, while none of the 33 sera from healthy Europeans and none of the 14 sera from patients with proven Rickettsia or Brucella infections reacted with the antigen. These results also show that an intracellular protein of Wolbachia endobacteria (WolAspAT) acts as antigen in human filariasis.