RESUMEN
BACKGROUND: Areca quid chewing is an etiological factor contributing to the development of oral cancer and pre-cancers, whose pathophysiology has been linked to inflammation and immune deterioration. Myeloid-derived suppressor cells (MDSC) play a key role in the regulation of immunity under certain pathological conditions, such as inflammation and cancer. As areca nut extracts (ANE) have been reported to induce a proinflammatory effect in antigen-stimulated mice, we hypothesized that ANE might enhance the development of MDSC. METHODS: Ovalbumin (OVA)-sensitized BALB/c mice were daily administered with ANE (5-50 mg/kg), polyphenol-enriched ANE (PANE; 25 mg/kg) or arecoline (5 mg/kg) by intraperitoneal injection for 10 doses. The mouse footpads were then subcutaneously challenged with OVA to induce local inflammatory responses. RESULTS: ANE and PANE treatment significantly increased the spleen index and the population of CD11b(+) Gr-1(+) cells in the spleen and peripheral blood, whereas arecoline was inactive. In addition, ANE and PANE treatment enhanced the expression of cytokines and enzymes associated with the immunosuppressive function of MDSC, including IL-10, arginase-I and iNOS in splenic CD11b(+) cells. Concordantly, ANE and PANE treatment augmented the infiltration of Gr-1(+) IL-10(+) cells in the footpads challenged with OVA. CONCLUSIONS: Our results suggested that areca nut constituents, in particular, polyphenols enhanced the development of myeloid-derived suppressor cells in vivo, which may be a critical mechanism linking inflammation and the compromised immunity reported to be associated with the pathophysiology of areca-related oral diseases.
Asunto(s)
Areca , Antígeno CD11b/efectos de los fármacos , Tolerancia Inmunológica/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Células Mieloides/efectos de los fármacos , Nueces , Extractos Vegetales/farmacología , Receptores de Quimiocina/efectos de los fármacos , Animales , Arecolina/farmacología , Arginasa/análisis , Peso Corporal , Antígeno CD11b/inmunología , Técnicas de Cultivo de Célula , Quimiotaxis de Leucocito/inmunología , Agonistas Colinérgicos/farmacología , Inmunización , Mediadores de Inflamación/inmunología , Interleucina-10/análisis , Leucocitos Mononucleares/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Monocitos/efectos de los fármacos , Monocitos/inmunología , Células Mieloides/inmunología , Óxido Nítrico Sintasa de Tipo II/análisis , Tamaño de los Órganos , Ovalbúmina/inmunología , Polifenoles/farmacología , Receptores de Quimiocina/inmunología , Bazo/efectos de los fármacos , Bazo/patologíaRESUMEN
Nonalcoholic steatohepatitis is characterized by the association of steatosis with hepatic cell injury, lobular inflammation and fibrosis. Curcumin is known for its antioxidant, anti-inflammatory and antifibrotic properties. The aim of this study was to test whether the administration of curcumin limits fibrogenic evolution in a murine model of nonalcoholic steatohepatitis. Male C57BL/6 mice were divided into four groups and fed a diet deficient in methionine and choline (MCD) or the same diet supplemented with methionine and choline for as long as 10 weeks. Curcumin (25 microg per mouse) or its vehicle (DMSO) was administered intraperitoneally every other day. Fibrosis was assessed by Sirius red staining and histomorphometry. Intrahepatic gene expression was measured by quantitative PCR. Hepatic oxidative stress was evaluated by staining for 8-OH deoxyguanosine. Myofibroblastic hepatic stellate cells (HSCs) were isolated from normal human liver tissue. The increase in serum ALT caused by the MCD diet was significantly reduced by curcumin after 4 weeks. Administration of the MCD diet was associated with histological steatosis and necro-inflammation, and this latter was significantly reduced in mice receiving curcumin. Curcumin also inhibited the generation of hepatic oxidative stress. Fibrosis was evident after 8 or 10 weeks of MCD diet and was also significantly reduced by curcumin. Curcumin decreased the intrahepatic gene expression of monocyte chemoattractant protein-1, CD11b, procollagen type I and tissue inhibitor of metalloprotease (TIMP)-1, together with protein levels of alpha-smooth muscle-actin, a marker of fibrogenic cells. In addition, curcumin reduced the generation of reactive oxygen species in cultured HSCs and inhibited the secretion of TIMP-1 both in basal conditions and after the induction of oxidative stress. In conclusion, curcumin administration effectively limits the development and progression of fibrosis in mice with experimental steatohepatitis, and reduces TIMP-1 secretion and oxidative stress in cultured stellate cells.
Asunto(s)
Curcumina/farmacología , Inhibidores Enzimáticos/farmacología , Hígado Graso/complicaciones , Cirrosis Hepática/etiología , Cirrosis Hepática/prevención & control , Actinas/antagonistas & inhibidores , Alanina Transaminasa/antagonistas & inhibidores , Alanina Transaminasa/sangre , Animales , Antígeno CD11b/efectos de los fármacos , Células Cultivadas , Quimiocina CCL2/antagonistas & inhibidores , Colina/administración & dosificación , Deficiencia de Colina , Colágeno Tipo I/antagonistas & inhibidores , Dieta , Células Estrelladas Hepáticas/metabolismo , Humanos , Hígado/metabolismo , Masculino , Metionina/administración & dosificación , Metionina/deficiencia , Ratones , Ratones Endogámicos C57BL , Músculo Liso/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Inhibidor Tisular de Metaloproteinasa-1/antagonistas & inhibidoresRESUMEN
AIM OF THE STUDY: Antrodia camphorata, a precious folkloric medicinal mushroom, has been used to treat tumorigenic diseases in Taiwan. This study was to investigate the innate immunity augmentation effects of different fractions prepared from hot water extracts of submerged cultured Antrodia camphorata (AC). MATERIALS AND METHODS: The cytokine induction potency of AC fraction in diluted peripheral blood culture was measured by ELISA. The effects of AC fraction on phagocytic activity and CD11b expression were measured by the ingestion of FITC-labeled Escherichia coli and by labeling with PE-labeled CD11b monoclonal antibody, respectively, using flow cytometry. The molecular mass of hot water-soluble polysaccharides and content of adenosine in AC fraction were determined by gel permeation chromatography (GPC) and HPLC, respectively. RESULTS: The mycelia fraction, Fr. M II, and culture filtrate fractions, Fr. E II and Fr. E III, showed the strongest TNF-alpha and IL-6 induction effect as a function of their concentration. These fractions (20mug/ml) also showed marked activity in enhancing phagocytosis in human polymorphonuclear neutrophils (PMN) and monocytes. In parallel, the expression of CD11b, an early marker of PMN activation, was also up-regulated dose-dependently. Composition analysis suggested that immunomodulatory effect of mycelia is mainly attributed to the 10-20kDa polysaccharides and adenosine. CONCLUSIONS: These results provide evidences that Antrodia camphorata can modulate innate immunity and may serve as an adjuvant for tumor treatment.
Asunto(s)
Antrodia/química , Antígeno CD11b/efectos de los fármacos , Factores Inmunológicos/inmunología , Adenosina/administración & dosificación , Adenosina/inmunología , Adenosina/aislamiento & purificación , Adulto , Antígeno CD11b/inmunología , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Medios de Cultivo , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Calor , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/aislamiento & purificación , Interleucina-6/metabolismo , Medicina Tradicional China , Micelio/química , Neutrófilos/inmunología , Fagocitosis/efectos de los fármacos , Polisacáridos/administración & dosificación , Polisacáridos/inmunología , Polisacáridos/aislamiento & purificación , Taiwán , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Trauma and hemorrhagic shock (T/HS) induce a systemic inflammatory response syndrome (SIRS). Neutrophils (polymorphonuclear leukocytes [PMN]) and other cells involved in acute lung injury (ALI) are activated by Ca2+ entry. Thus, inhibiting Ca2+ entry might attenuate post-traumatic lung injury. Inhibiting voltage-operated (L-type) Ca2+ channels during shock could cause cardiovascular collapse, but PMN are "nonexcitable" cells, lack L-type channels, and mobilize Ca2+ via nonspecific channels. We previously showed that PMN Ca2+ entry requires sphingosine 1-phosphate synthesis by sphingosine kinase and that both sphingosine kinase inhibition and blockade of nonspecific channels attenuate ALI when begun before shock. Pretreatment for clinical injuries, however, is impractical. Therefore, we now studied whether Ca2+ entry inhibition that begun during resuscitation from T/HS could attenuate SIRS and ALI without causing hemodynamic compromise. Male Sprague-Dawley rats underwent laparotomy and fixed-pressure shock (mean arterial pressure, 35 +/- 5 mmHg; 90 min). Sphingosine kinase inhibition or nonspecific Ca2+ channel inhibition was begun after resuscitation with 10% of shed blood. We then studied in vivo PMN activation and associated lung injury in the presence or absence of Ca2+ entry inhibition. Neither treatment worsened shock. Each treatment decreased CD11b expression, respiratory burst, PMN p38 MAP-kinase phosphorylation, PMN sequestration, and lung capillary leak in vivo. The similar results seen with two different forms of inhibition strengthen the conclusion that the biological effects seen were specific for calcium entry inhibition. Ca2+ entry inhibition is a candidate therapy for management of lung injury after shock.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Neumonía/prevención & control , Choque Hemorrágico/tratamiento farmacológico , Choque Traumático/tratamiento farmacológico , Aminofenoles/farmacología , Aminofenoles/uso terapéutico , Animales , Antígeno CD11b/efectos de los fármacos , Calcio/sangre , Permeabilidad Capilar/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Masculino , Neutrófilos/efectos de los fármacos , Nitrendipino/análogos & derivados , Nitrendipino/farmacología , Nitrendipino/uso terapéutico , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Estallido Respiratorio/efectos de los fármacos , Tiazoles/farmacología , Tiazoles/uso terapéutico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Prolonged induction of excessive levels of inflammatory mediators contributes to the pathogenesis of chronic disease states, such as periodontitis. It is thus important to develop safe and effective anti-inflammatory strategies for therapeutic reasons. In this study, we determined the ability of aqueous extracts from elder flower (Sambucus nigra) to inhibit the proinflammatory activity of major virulence factors from the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. METHODS: Monocytes/macrophages or neutrophils were incubated with whole cells of P. gingivalis, A. actinomycetemcomitans, or purified components thereof (lipopolysaccharide and fimbriae) in the absence or presence of elder flower extract and were assayed for cytokine production, integrin activation, or induction of the oxidative burst. RESULTS: The elder flower extract was found to potently inhibit all proinflammatory activities tested. Investigation of the underlying mechanisms revealed that the anti-inflammatory extract inhibited activation of the nuclear transcription factor kappaB and of phosphatidylinositol 3-kinase. CONCLUSION: The elder flower extract displays useful anti-inflammatory properties that could be exploited therapeutically for the control of inflammation in human periodontitis.
Asunto(s)
Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Antiinflamatorios/farmacología , Flores , Mediadores de Inflamación/antagonistas & inhibidores , Extractos Vegetales/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Sambucus nigra , Aggregatibacter actinomycetemcomitans/inmunología , Animales , Antígeno CD11b/efectos de los fármacos , Antígenos CD18/efectos de los fármacos , Fimbrias Bacterianas/inmunología , Humanos , Interleucinas/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Monocitos/efectos de los fármacos , Monocitos/inmunología , FN-kappa B/antagonistas & inhibidores , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Porphyromonas gingivalis/inmunología , Estallido Respiratorio/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factores de Virulencia/antagonistas & inhibidoresRESUMEN
OBJECTIVES: This study investigated the effects of glutamine (Gln) on plasma intracellular adhesion molecule-1 levels and leukocyte integrin (CD11a/CD18 and CD11b/CD18) expressions in gut-derived sepsis. Myeloperoxidase (MPO) activities in organs were also analyzed to identify the extent of tissue injury resulting from neutrophil infiltration. METHODS: Mice were randomly assigned to a normal group (NC), a control group, or a Gln group. The NC group was fed standard chow diet; the control group was fed a common semipurified diet; and the Gln group received a diet in which part of the casein was replaced by Gln, which provided 25% of total amino acid nitrogen. After 3 wk, sepsis was induced by cecal ligation and puncture (CLP) in the control and Gln groups. Mice in the experimental groups were killed at 0, 6, 12, and 24 h after CLP. Mice in the NC group were killed when CLP was performed. Blood and organ samples were collected for further analysis. RESULTS: Plasma intracellular adhesion molecule-1 levels were significantly lower in the Gln group than in the control group at 6, 12, and 24 h after CLP. Expressions of lymphocyte CD11a/CD18 were significantly higher, whereas polymorphonuclear lymphocyte expressions of CD11b/CD18 were lower in the Gln group than in the corresponding control group at 6 and 12 h after CLP. In comparisons of MPO activities in various organs, the Gln group had lower MPO activities at 6 and 12 h in the lung, at 6, 12, and 24 h in the liver, at 12 and 24 h in the kidneys, and at 12 h in the intestine than those in the control group. CONCLUSIONS: Results of this study demonstrate that a Gln-supplemented enteral diet increased lymphocyte CD11a/CD18 expressions, whereas neutrophil CD11b/CD18 expressions, circulating intracellular adhesion molecule-1 levels, and MPO activities in various organs decreased with gut-derived sepsis. These findings suggest that, under septic conditions, Gln administration may enhance lymphocyte function, attenuate interactions between polymorphonuclear lymphocytes and endothelium, and thus may decrease neutrophil infiltration into tissues.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Glutamina/uso terapéutico , Molécula 1 de Adhesión Intercelular/metabolismo , Peroxidasa/metabolismo , Sepsis/inmunología , Animales , Antígeno CD11a/efectos de los fármacos , Antígeno CD11a/inmunología , Antígeno CD11a/metabolismo , Antígeno CD11b/efectos de los fármacos , Antígeno CD11b/inmunología , Antígeno CD11b/metabolismo , Antígenos CD18/efectos de los fármacos , Antígenos CD18/inmunología , Antígenos CD18/metabolismo , Suplementos Dietéticos , Regulación de la Expresión Génica/inmunología , Glutamina/administración & dosificación , Masculino , Ratones , Ratones Endogámicos ICR , Infiltración Neutrófila , Distribución Aleatoria , Sepsis/metabolismoRESUMEN
OBJECTIVE: To assess the effects of taking the "Pingzhi Tablets" on infiltration of inflammatory in tissues of chronic sinusitis and nasal polyps. METHOD: Nasal polyps from taking the "Pingzhi Tablets" treated patients (40 cases) and untreated patients (40 cases) were investigated. The samples were stained by HE and SABC-AP immunohistochemical methods. RESULT: Compared with untreated polyps, the polyps treated by taking the "Pingzhi Tablets" contained significantly lower tissue densities of CD 11b+, CD7+ positive cells. Although the densities of CD 19+ positive cells were lower in treated polyps, the differences were not statistically significant. CONCLUSION: The findings demonstrated tissue effects of treatment with taking "Pingzhi Tablets" and the treatment was effective in suppressing the inflammatory cell infiltration.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Pólipos Nasales/tratamiento farmacológico , Fitoterapia , Sinusitis/tratamiento farmacológico , Adulto , Anciano , Antígenos CD19/efectos de los fármacos , Antígenos CD7/efectos de los fármacos , Antígeno CD11b/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/patología , Sinusitis/patologíaRESUMEN
The incidence of myocardial infarction in patients who have the aquired immunodeficiency syndrome (AIDS) is increasing. However, no effective therapeutic agents have been discovered to reduce myocardial ischemia-reperfusion (I/R) injury in pathologies associated with AIDS. The aim of this study was to determine if infarct size is increased in murine AIDS after I/R injury and if I/R injury could be attenuated with vitamin E supplementation. Three groups of mice were studied: control, murine AIDS, and murine AIDS with vitamin E supplementation. Anesthetized mice were subjected to 30 min of left anterior descending coronary artery occlusion and 120 min of reperfusion. The hearts in mice that had murine AIDS had a larger infarct size compared to controls after I/R injury. Vitamin E supplementation significantly reduced infarct size and inhibited polymorphonuclear neutrophil (PMN) CD11b expression (p < 0.05). However, vitamin E supplementation did not affect PMN reactive oxygen species (ROS) production and platelet CD62p expression. These results suggest that the reduction of myocardial I/R injury with vitamin E supplementation may be the result of the inhibition of PMN CD11b expression. Vitamin E may be a promising prophylactic agent for the reduction of the severity of myocardial I/R injury in patients who have AIDS.