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1.
Clinics (Sao Paulo) ; 69(9): 621-6, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25318094

RESUMEN

OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1ß and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus.


Asunto(s)
Inhibidores de la Ciclooxigenasa/farmacología , Hipocampo/efectos de los fármacos , Indometacina/farmacología , Monocinas/efectos de los fármacos , Receptores de Bradiquinina/efectos de los fármacos , Estado Epiléptico/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Interleucina-1beta/análisis , Interleucina-1beta/efectos de los fármacos , Masculino , Monocinas/análisis , Pilocarpina , Ratas Wistar , Receptor de Bradiquinina B1/análisis , Receptor de Bradiquinina B1/efectos de los fármacos , Receptor de Bradiquinina B2/análisis , Receptor de Bradiquinina B2/efectos de los fármacos , Receptores de Bradiquinina/análisis , Estado Epiléptico/inducido químicamente , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/efectos de los fármacos
2.
Clinics ; 69(9): 621-626, 9/2014. graf
Artículo en Inglés | LILACS | ID: lil-725409

RESUMEN

OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. .


Asunto(s)
Animales , Masculino , Inhibidores de la Ciclooxigenasa/farmacología , Hipocampo/efectos de los fármacos , Indometacina/farmacología , Monocinas/efectos de los fármacos , Receptores de Bradiquinina/efectos de los fármacos , Estado Epiléptico/tratamiento farmacológico , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Interleucina-1beta/análisis , Interleucina-1beta/efectos de los fármacos , Monocinas/análisis , Pilocarpina , Ratas Wistar , Receptor de Bradiquinina B1/análisis , Receptor de Bradiquinina B1/efectos de los fármacos , /análisis , /efectos de los fármacos , Receptores de Bradiquinina/análisis , Estado Epiléptico/inducido químicamente , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/efectos de los fármacos
4.
J Leukoc Biol ; 80(4): 744-52, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16855064

RESUMEN

Macrophages phagocytose apoptotic cells without causing neutrophil infiltration in vivo under physiological conditions. Our recent study, however, showed that macrophages produce IL-8 or MIP-2, a murine IL-8 homologue, upon coculturing with apoptotic cells, indicating that there must be unknown mechanisms for preventing IL-8 or MIP-2 production. As activated macrophages produce NO to regulate inflammation, we examined the NO production by macrophages upon coculturing with apoptotic or necrotic cells and explored the role of NO in MIP-2 production. NO was produced on coculturing with early apoptotic cells much more significantly than with late apoptotic or necrotic cells. On the contrary, MIP-2 was produced on coculturing with late apoptotic or necrotic cells much more significantly than with early apoptotic cells. N(G)-Nitro-L-arginine methyl ester, an inhibitor of NO synthase, or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a scavenger of NO, augmented MIP-2 production on coculturing with early apoptotic cells. The addition of N-ethylethanamine:1,1-diethyl-2-hydroxy-2-nitrosohydrazine [1:1], a donor of NO, conversely, caused suppression of MIP-2 production on coculturing with late apoptotic cells. These results suggest an important role of NO for preventing MIP-2 production by macrophages upon coculturing with early apoptotic cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Técnicas de Cocultivo/métodos , Macrófagos/efectos de los fármacos , Monocinas/biosíntesis , Óxido Nítrico/fisiología , Animales , Apoptosis/inmunología , Línea Celular , Quimiocina CXCL2 , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Células HL-60 , Humanos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Monocinas/efectos de los fármacos , Monocinas/inmunología , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/farmacología , Relación Estructura-Actividad
5.
Alcohol Clin Exp Res ; 29(11 Suppl): 146S-150S, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16344600

RESUMEN

Chronic ethanol-induced liver injury follows a typical progression from its earliest stage of steatosis to more advanced injury, characterized by the development of inflammation, hepatocyte necrosis/apoptosis, fibrosis and finally cirrhosis. Kupffer cells, the resident macrophage in the liver, play a critical role in the progression of liver injury. Increased exposure of Kupffer cells to lipopolysaccharide (LPS) during chronic ethanol exposure leads to the production of a number of inflammatory mediators, including tumor necrosis factor alpha (TNF-alpha). Recent evidence indicates that in addition to increased exposure to LPS, Kupffer cells also develop an enhanced sensitivity to LPS after chronic ethanol feeding. We have recently identified early growth response-1 (Egr-1), an immediate-early gene transcription factor, as an important contributor to increased LPS-stimulated TNF-alpha secretion by Kupffer cells after chronic ethanol exposure. In other models of tissue injury, such as ischemia-reperfusion in the lung, Egr-1 acts as a coordinator of the complex response to stress. Here we review the literature regarding the role of EGR-1 in regulation of a number of genes implicated in each of the stages of chronic ethanol-induced liver injury. In addition to the critical role of Egr-1 in generating maximal LPS-stimulated TNF-alpha expression, Egr-1 also controls the expression of a number of inflammatory mediators, including intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-2, as well as genes contributing to fibrosis, such as transforming growth factor (TFG)-beta1, platelet-derived growth factor PDGF-A chain and fibroblast growth factor (FGF). Understanding the contribution of Egr-1 to the expression of genes involved in the development of chronic ethanol-induced liver injury may lead to the development of improved therapies designed to prevent and/or reverse alcohol-induced liver injury.


Asunto(s)
Proteína 1 de la Respuesta de Crecimiento Precoz/fisiología , Etanol/toxicidad , Hepatopatías Alcohólicas/fisiopatología , Hígado/fisiopatología , Animales , Quimiocina CCL2/efectos de los fármacos , Quimiocina CXCL2 , Proteína 1 de la Respuesta de Crecimiento Precoz/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Molécula 1 de Adhesión Intercelular/efectos de los fármacos , Macrófagos del Hígado/efectos de los fármacos , Lipopolisacáridos/farmacología , Hígado/patología , Hepatopatías Alcohólicas/patología , Monocinas/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacos
6.
J Heart Lung Transplant ; 24(1): 38-45, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15653377

RESUMEN

BACKGROUND: Macrophages play an important role in ischemia-reperfusion injury of various organs. Liposome-encapsulated dichloromethylene diphosphonate (clodronate-liposome) depletes local macrophages in vivo. However, the effect of this approach on alveolar macrophages in pulmonary ischemia-reperfusion injury has not yet been evaluated. METHODS: Clodronate-liposomes in Hanks' balanced salt solution (HBSS) or HBSS alone were given intratracheally to anesthetized male Lewis rats in the clodronate or the control group (n = 6/each group). After 3 days, we subjected the lungs to ischemia (37 degrees C, 60 minutes) and reperfusion (60 minutes) in an isolated blood-perfused rat lung model. Analysis during reperfusion included gas exchange, hemodynamics, and airway mechanics. At the end of reperfusion, we determined leukocyte recruitment and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. RESULTS: In the clodronate group, 4 experiments had to be terminated within 10 minutes of reperfusion because of severe lung injury, whereas all lungs of the controls could be studied during the 60-minute reperfusion period (p < 0.05). Clodronate significantly decreased dynamic airway compliance (p < 0.05) and increased airway resistance. Besides a tendency toward greater pulmonary vascular resistance, this was associated with recruitment of polymorphonuclear neutrophils (p < 0.05) and increased MIP-2 concentrations in the bronchoalveolar lavage fluid (p < 0.05). CONCLUSIONS: Intratracheal administration of liposome-encapsulated clodronate does not benefit, but aggravates, warm ischemia-reperfusion injury of the lung, increasing MIP-2-associated alveolar neutrophil recruitment and airway mechanical dysfunction.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Ácido Clodrónico/administración & dosificación , Pulmón/citología , Pulmón/patología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Daño por Reperfusión/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CXCL2 , Modelos Animales de Enfermedad , Liposomas , Pulmón/fisiopatología , Rendimiento Pulmonar/efectos de los fármacos , Masculino , Modelos Cardiovasculares , Monocinas/efectos de los fármacos , Monocinas/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Ratas , Ratas Endogámicas Lew , Resistencia Vascular/efectos de los fármacos
8.
Am J Respir Crit Care Med ; 166(7): 954-60, 2002 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-12359653

RESUMEN

To test whether a serine elastase inhibitor could prevent or reduce emphysema, we exposed guinea pigs to cigarette smoke acutely, or daily for 6 months, and treated some animals with the neutrophil elastase inhibitor ZD0892. Acute smoke exposure increased lavage neutrophils and increased desmosine and hydroxyproline, measures of elastin and collagen breakdown; all these measures were reduced by ZD0892. Long-term smoke exposure produced emphysema and increases in lavage neutrophils, desmosine, hydroxyproline, and plasma tumor necrosis factor alpha (TNF-alpha). ZD0892 treatment returned lavage neutrophils, desmosine, and hydroxyproline levels to control values, and decreased airspace enlargement by 45% and TNF-alpha by 30%. Animals exposed to smoke for 4 months and then to smoke plus ZD0892 for 2 months were not protected against emphysema. Mice exposed to smoke showed increases in gene expression of neutrophil chemoattractant macrophage inflammatory protein-2, macrophage chemoattractant protein-1, and TNF-alpha at 2 hours along with increased plasma TNF-alpha; ZD0892 prevented the increases in macrophage inflammatory protein-2 and macrophage chemoattractant protein-1 expression and reduced plasma TNF-alpha levels to baseline. These data demonstrate that a serine elastase inhibitor ameliorates the inflammatory and destructive effects of cigarette smoke, and that these effects are mediated in part by neutrophils and by smoke-driven TNF-alpha production.


Asunto(s)
Enfisema Pulmonar/tratamiento farmacológico , Enfisema Pulmonar/etiología , Serpinas/administración & dosificación , Contaminación por Humo de Tabaco/efectos adversos , Animales , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CCL8 , Quimiocina CXCL2 , Desmosina/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Cobayas , Hidroxiprolina/efectos de los fármacos , Hidroxiprolina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Quimioatrayentes de Monocitos/genética , Proteínas Quimioatrayentes de Monocitos/metabolismo , Monocinas/efectos de los fármacos , Monocinas/genética , Monocinas/metabolismo , Neutrófilos/efectos de los fármacos , Enfisema Pulmonar/sangre , Factores de Tiempo , Transcripción Genética/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
9.
Eur J Pharmacol ; 432(1): 107-19, 2001 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-11734194

RESUMEN

In this report, we describe experiments in which cannabinoid receptor ligands were evaluated for effects on the development of a peritoneal inflammation when elicited in mice with thioglycollate broth or staphylococcus enterotoxin A. The cannabinoid receptor agonists [(-)-11-hydoxy-Delta(8) tetrahydrocannabinol-dimethylheptyl] (HU-210) and [(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl[pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthalenyl) methanone] (WIN 55212-2) blocked the migration of neutrophils into the peritoneal cavity in response to these inflammatory stimuli. This effect was caused by a delay in the production of the neutrophil chemoattractants, KC and macrophage inflammatory protein-2. HU-210 and WIN 55212-2 blocked neutrophil chemokines and neutrophil migration whether administered subcutaneously (s.c.) or intracerebroventricularly (i.c.v.). Their modulatory effects on the inflammation were antagonized by centrally administered [N-(piperdin-1-yl)-5-(4-chloropheny)-1-(2,4-dichloropheny)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] (SR141716A), a selective cannabinoid CB(1) receptor antagonist. This latter observation, and the ability of the cannabinoid receptor agonists to suppress the peritoneal inflammation at relatively low doses when administered i.c.v., indicated a role for central cannabinoid CB(1) receptors in the anti-inflammatory activities of HU-210 and WIN 55212-2. The cannabinoid receptor agonists had no effect on monocyte migration elicited by thioglycollate, despite their ability to suppress monocyte chemotactic protein-1 levels in lavage fluids. The cannabinoid CB(2) receptor antagonist, [N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-choro-3 methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide] (SR144528) inhibited the peritoneal inflammation in a manner analogous to that of HU-210 and WIN 55212-2 when administered i.c.v., but it did not appear to act through central cannabinoid CB(1) receptors. The present results add to the body of literature indicating that cannabinoid receptor ligands have diverse anti-inflammatory properties.


Asunto(s)
Antiinflamatorios/farmacología , Dronabinol/farmacología , Morfolinas/farmacología , Naftalenos/farmacología , Peritonitis/prevención & control , Receptores de Droga/metabolismo , Animales , Líquido Ascítico/química , Líquido Ascítico/citología , Benzoxazinas , Movimiento Celular/efectos de los fármacos , Quimiocina CCL2/metabolismo , Quimiocina CXCL2 , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Dronabinol/análogos & derivados , Enterotoxinas/administración & dosificación , Femenino , Genotipo , Ligandos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Monocinas/efectos de los fármacos , Monocinas/metabolismo , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Peritonitis/inducido químicamente , Peritonitis/patología , Receptores de Cannabinoides , Receptores de Droga/agonistas , Receptores de Droga/genética , Organismos Libres de Patógenos Específicos , Tioglicolatos/administración & dosificación
10.
Neuroimmunomodulation ; 6(4): 261-83, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10393513

RESUMEN

Muramyl peptides are fragments of peptidoglycan from the cell walls of bacteria. Because of their unique chemistry, the immune system recognizes that muramyl peptides are products of bacteria, and it responds by becoming activated to resist infection. This resistance to infection is nonspecific, and extends to unrelated species of bacteria, fungi, and viruses. A key mechanism of the resistance to infection is activation of macrophages. Macrophage activation results in increased production of microbicidal oxygen radicals like superoxide and peroxide, and in increased secretion of inflammatory cytokines like interleukin-1beta and tumor necrosis factor-alpha. These cytokines, besides activating neutrophils, B lymphocytes, and T lymphocytes, act on the central nervous system to induce physiological responses like fever and sleep. These physiological responses also aid in combating infection. Muramyl peptides also activate macrophages and other cells of the immune system to kill cancer cells. Muramyl peptides and similar agents will become more important as therapeutic agents in the future, due to increasing resistance of microbes to antibiotics, and increasing numbers of patients with immunodeficiencies.


Asunto(s)
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Macrófagos/efectos de los fármacos , Monocinas/efectos de los fármacos , Ácidos Murámicos/farmacología , Peptidoglicano/química , Sueño/efectos de los fármacos , Acetilmuramil-Alanil-Isoglutamina/farmacología , Animales , Secuencia de Carbohidratos , Humanos , Sistema Inmunológico/citología , Sistema Inmunológico/efectos de los fármacos , Datos de Secuencia Molecular
11.
J Periodontal Res ; 34(7): 370-3, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10685363

RESUMEN

The impact of lipoxin A4 (LXA4) and aspirin-triggered-lipoxins (ATL) was investigated in tumor necrosis factor (TNF alpha)-initiated neutrophil (PMN) responses in vitro and in vivo using LX analogs that are metabolically more stable. At nanomolar levels, the LXA4 and ATL analog 15 R/S-methyl-LXA4 each blocked TNF alpha-stimulated IL-1 beta release by isolated human PMN in vitro. These LXA4-ATL actions were time- and concentration-dependent. The TNF alpha-induced IL-1 beta gene expression was also regulated by 15 R/S-methyl-LXA4. In addition, 15 R/S-methyl-LXA4 added to murine air pouches dramatically inhibited TNF alpha-stimulated leukocyte trafficking in vivo, as well as altered the appearance of both macrophage inflammatory peptide-2 and IL-1 beta and concomitantly stimulated IL-4 in pouch exudates. These findings from in vitro and in vivo experiments indicate that both LXA4 and ATL are regulators of TNF alpha-directed neutrophil actions and stimulate IL-4 in exudates and thus regulate mediators that are held to play an important role in the pathogenesis of periodontal disease.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Ácidos Hidroxieicosatetraenoicos/farmacología , Lipoxinas , Neutrófilos/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Animales , Quimiocina CXCL2 , Quimiocinas/antagonistas & inhibidores , Factores Quimiotácticos/antagonistas & inhibidores , Citocinas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-1/antagonistas & inhibidores , Interleucina-1/genética , Interleucina-4/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Monocinas/efectos de los fármacos , Infiltración Neutrófila/efectos de los fármacos , Enfermedades Periodontales/etiología , Enfermedades Periodontales/inmunología , Estereoisomerismo
12.
Am J Respir Cell Mol Biol ; 15(1): 97-106, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8679228

RESUMEN

To understand the basis for the refractory nature of acute respiratory distress syndrome (ARDS) to glucocorticoids, the effects of dexamethasone pretreatment (DEX, 2 mg/kg, intraperitoneally) on the kinetics of airway tumor necrosis factor-alpha (TNF alpha) and macrophage inflammatory protein 2 (MIP-2) production, and polymorphonuclear leukocyte (PMN) influx after intratracheal lipopolysaccharide (LPS) (1 mg/kg) in rats were investigated. In the absence of exogenous glucocorticoids, TNF alpha and MIP-2 levels in bronchoalveolar lavage (BAL) fluid peaked at 21 and 300 ng, respectively, by 3 h. DEX pretreatment resulted in a 74% reduction in BAL TNF alpha, yet MIP-2 accumulation was unchanged. In addition, DEX reduced PMN influx at 5 h by 58.4% to 4.1 +/- 0.7 x 10(6) PMN (n = 5). DEX, however, did not mitigate the 3-fold increase in total BAL protein observed at 5 h, attributable to albumin influx. The effects of subacute DEX treatment (3.8 mg/kg per day, for 3 days) on cell-surface expression of the adhesion molecules CD11a, CD11b, and L-selectin were determined by flow cytometric analysis of peripheral blood and autologous BAL PMN. Compared with peripheral blood PMN, exudative PMN had 4-fold greater CD11b expression, no change in CD11a, and loss of L-selectin immunoreactivity 5 h after LPS challenge. The upregulation of CD11b on exudative PMN was insensitive to DEX pretreatment, which, together with a failure to suppress MIP-2 levels, provides a possible explanation for the lack of efficacy of steroids in the management of ARDS.


Asunto(s)
Dexametasona/farmacología , Glucocorticoides/farmacología , Mediadores de Inflamación/análisis , Integrinas/biosíntesis , Neutrófilos/inmunología , Animales , Especificidad de Anticuerpos , Antígenos CD1/metabolismo , Peso Corporal/efectos de los fármacos , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/efectos de los fármacos , Quimiocina CXCL2 , Modelos Animales de Enfermedad , Endotoxinas , Citometría de Flujo , Cinética , Selectina L/inmunología , Selectina L/metabolismo , Recuento de Leucocitos , Lipopolisacáridos/farmacología , Macrófagos Alveolares/química , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/inmunología , Masculino , Monocinas/biosíntesis , Monocinas/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Elastasa Pancreática/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/patología , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/efectos de los fármacos
13.
Kidney Int ; 49(1): 236-43, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8770974

RESUMEN

Several studies support the hypothesis that bacterial contamination of the dialysate stimulates the inflammatory response to hemodialysis (HD) and increases the long-term morbidity of HD patients; this phenomenon could also be modulated by the nature of the HD membrane. Therefore, this study was designed to compare the effects of non-sterile (NSBD, mean endotoxin content +/- SEM 97 +/- 22 EU/ml) and ultrapure bicarbonate dialysate (UPBD, sterile and pyrogen-free, obtained by ultrafiltration through polyamide) on several aspects of the inflammatory reaction during in vitro HD. The HD sessions (7 in each experimental group) were performed using miniaturized new cuprophane (CU) and polyacrylonitrile (PAN) hollow fiber dialyzers, and closed dialysate and blood circuits (the latter filled with heparinized blood from healthy donors). Plasma C3aDesarg levels were significantly increased after 15 minutes (t1) and increased further after three hours (t2) of CU HD, while during PAN dialysis they decreased from t0 to t1 and t2; however, no difference appeared between experiments with NSBD and UPBD. Granulocyte (PMN) and monocyte (MNC) expression of LFA-1, Mac-1, and CD45 at the start (t0), t1 and t2 was quantitated by flow cytometry analysis, after staining of the cells with specific fluorescinated monoclonal antibodies. In contrast with published data of in vivo HD, LFA-1 was overexpressed at t1 and peaked at t2, which suggests that the leukocytes expressing more LFA-1 leave the systemic circulation during in vivo HD. During CU HD, Mac-1 and CD45 on PMN and MNC were significantly increased at t1, and still more at t2. During PAN HD, Mac-1 and CD45 remained unchanged at t1, but increased significantly at t2 on PMN as on MNC. Again, no significant difference was found between NSBD and UPBD in LFA-1, Mac-1 and CD45 expression on PMN and MNC, during both CU and PAN HD. AFter three hours of dialysis, plasma levels of TNF-alpha, but not of IL-6, were significantly increased with CU and PAN. Again, no difference appeared when NSBD and UPBD were compared. Moreover, the lack of influence of bacterial contamination of the dialysate on TNF-alpha production was confirmed when MNC were cultured up to 24 hours after the end of the HD session. We conclude that complement activation products, either in plasma (CU) of those adsorbed on the HD membrane (CU and PAN) play the major role in the overexpression of beta 2-integrins and CD45 by PMN and MNC during HD. Also, bacterial products (at the levels that can be found in clinical conditions) do not influence either beta 2-integrin overexpression or TNF-alpha production induced by the dialysis membrane.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Soluciones para Diálisis/efectos adversos , Granulocitos/metabolismo , Inflamación/etiología , Monocitos/metabolismo , Monocinas/biosíntesis , Diálisis Renal , Adulto , Moléculas de Adhesión Celular/efectos de los fármacos , Femenino , Granulocitos/inmunología , Humanos , Inflamación/metabolismo , Inflamación/patología , Antígenos Comunes de Leucocito/metabolismo , Antígeno-1 Asociado a Función de Linfocito/metabolismo , Antígeno de Macrófago-1/metabolismo , Masculino , Monocitos/inmunología , Monocinas/efectos de los fármacos
14.
Tsitologiia ; 38(3): 397-402, 1996.
Artículo en Ruso | MEDLINE | ID: mdl-8768108

RESUMEN

Effects of AML and normal mononuclear phagocyte conditioned media (CM) on the proliferation and differentiation of monoblastic human cell line U-937 have been studied. The normal mononuclear phagocyte CM inhibited proliferation and weakly stimulated differentiation of U-937 cells, whereas AML CM exerted no effect. Activation of both normal and AML macrophages with phorbol ether (TPA) was followed by enhancement of CM effect. TPA treatment corrected defects of secretory activity of AML mononuclear phagocytes. A possible role of different monokines in the regulation of proliferation and differentiation of leukaemic cells is discussed.


Asunto(s)
Leucemia Mieloide Aguda/inmunología , Macrófagos/metabolismo , Monocitos/metabolismo , Monocinas/farmacología , Células de la Médula Ósea , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Humanos , Linfoma de Células B Grandes Difuso , Macrófagos/efectos de los fármacos , Monocitos/efectos de los fármacos , Monocinas/efectos de los fármacos , Monocinas/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Células Tumorales Cultivadas
15.
Am J Reprod Immunol ; 34(4): 231-5, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8579760

RESUMEN

PROBLEM: Inflammation of human gestational tissues is a key pathophysiologic event in the genesis of infection-associated preterm labor. Human gestational tissues produce several inflammatory cytokines after stimulation with bacterial products. These include interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), and IL-6. Another class of cytokines includes chemokines of the "C-C" subclassification such as macrophage inflammatory protein-1 alpha (MIP-1 alpha). The purpose of this study was to determine whether cultured human decidual cells produce MIP-1 alpha in response to other inflammatory cytokines. METHODS: Various concentrations of IL-1 beta, TNF alpha, IL-6, and IL-4 were incubated with confluent monolayer cultures of decidual cells isolated from normal term placentae for 16 h at 37 degrees C, and MIP-1 alpha concentrations in culture supernatants were measured by ELISA. RESULTS: We found that incubation of decidual cells with IL-1 beta, TNF alpha, and IL-4 resulted in significant concentration-dependent increases in MIP-1 alpha production. IL-6 had no effect on MIP-1 alpha production. CONCLUSIONS: Our data are the first to show that human decidual cells in culture produce MIP-1 alpha in response to other inflammatory cytokines. We suggest that decidual cell production of MIP-1 alpha is an important early event in the pathophysiology of infection-associated preterm labor.


Asunto(s)
Decidua/efectos de los fármacos , Decidua/metabolismo , Mediadores de Inflamación/farmacología , Monocinas/biosíntesis , Monocinas/efectos de los fármacos , Células Cultivadas , Quimiocina CCL4 , Decidua/citología , Femenino , Humanos , Interleucina-1/farmacología , Interleucina-4/farmacología , Interleucina-6/farmacología , Interleucinas/farmacología , Proteínas Inflamatorias de Macrófagos , Embarazo , Factor de Necrosis Tumoral alfa/farmacología
16.
Br J Haematol ; 89(2): 258-65, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7873375

RESUMEN

Human myeloid leukaemia cell lines have been shown to differentiate into distinct cell lineages in vitro in response to several differentiation-inducing agents. A human eosinophilic leukaemia cell line, EoL-1, has been shown to differentiate into mature eosinophilic granulocytes by treatment with the culture supernatant of a human T-cell line, HIL-3. In this study we have studied whether the EoL-1 cell line has potential to differentiate into cell lineage other than eosinophils. We found that EoL-1 cells cultured in the presence of tumour necrosis factor (TNF)-alpha (10 u/ml) and interferon (IFN)-gamma (1000 u/ml) for 2-4 d differentiated into macrophage-like cells in morphology, and expressed CD14 antigen on their cell surface. It is possible that the small subpopulation of EoL-1 cells which contains non-specific esterase (NSE) activity may be preferentially differentiated by TNF-alpha and IFN-gamma. To clarify this issue, we have cloned the EoL-1 cell line and obtained NSE negative and positive sublines. Both EoL-1 sublines differentiated into monocyte/macrophage-like cells, because: (a) EoL-1 sublines were induced to express CD14 antigen, and (b) they attached firmly to the plastic wells; (c) after differentiation they became strongly positive for NSE staining, and secreted TNF-alpha in response to the stimulation with lipopolysaccharide; and (d) they exhibited potent phagocytic activity. Therefore, we found that the EoL-1 cell line has the ability to differentiate not only into mature eosinophilic cells but also into monocyte/macrophage cell lineage, suggesting that EoL-1 cells represent immature cells with ability to differentiate into multiple cell lineages.


Asunto(s)
Síndrome Hipereosinofílico/patología , Interferón gamma/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Antígenos CD11/metabolismo , Diferenciación Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Macrófagos/efectos de los fármacos , Monocitos/efectos de los fármacos , Monocinas/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Receptores del Factor de Necrosis Tumoral/metabolismo , Proteínas Recombinantes/farmacología , Células Tumorales Cultivadas
17.
Am J Respir Cell Mol Biol ; 10(1): 8-15, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8292385

RESUMEN

A number of disease states are characterized by the accumulation of inflammatory cells at the site of tissue injury. Mononuclear phagocytes (M phi) represent key cellular mediators of inflammation via the production of regulatory and chemokinetic cytokines. One such cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), has been shown to be one of the major inducible chemotaxins expressed from murine macrophage cell lines (RAW 264.7). We postulated that MIP-1 alpha is a major monocyte chemoattractant produced by resident M phi, and the magnitude of production of this chemotaxin may depend upon the specific population of M phi studied. To test this hypothesis, we isolated alveolar macrophages (AM phi) and peritoneal macrophages (PM phi) from CD-1 mice by bronchoalveolar and peritoneal lavage, respectively. Recombinant murine MIP-1 alpha accounted for significant neutrophil chemokinetic rather than chemotactic activity, as assessed by checkerboard analysis. LPS-stimulated AM phi-derived monocyte chemotactic activity (MCA) was significantly neutralized by specific rabbit anti-murine MIP-1 alpha serum. In contrast, PM phi-derived conditioned media failed to produce MCA attributable to MIP-1 alpha. The production of MIP-1 alpha was then characterized from both AM phi and PM phi. While unstimulated AM phi and PM phi failed to express MIP-1 alpha mRNA, both AM phi and PM phi challenged with lipopolysaccharide (LPS) expressed MIP-1 alpha mRNA in a time-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Citocinas/inmunología , Macrófagos Alveolares/inmunología , Macrófagos Peritoneales/inmunología , Monocinas/inmunología , Animales , Quimiocina CCL4 , Quimiotaxis de Leucocito/inmunología , Citocinas/biosíntesis , Citocinas/efectos de los fármacos , Dexametasona/farmacología , Dinoprostona/farmacología , Humanos , Cinética , Lipopolisacáridos/farmacología , Proteínas Inflamatorias de Macrófagos , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Ratones , Monocitos/inmunología , Monocinas/biosíntesis , Monocinas/efectos de los fármacos , Neutrófilos/inmunología , ARN Mensajero/biosíntesis
18.
Rheumatol Int ; 14(1): 21-5, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7939136

RESUMEN

Recombinant human interleukin-4 (rhIL-4) and rhIL-1 alpha each produced a rapid down-modulation of tumour necrosis factor receptor (TNFR) on rheumatoid synovial fibroblasts (RSF) in vitro. This was associated with a staurosporine-resistant increase in p55 soluble TNFR levels, in culture media, suggesting that down-modulation was due to enhanced receptor shedding via a protein kinase C-independent mechanism. Pretreatment with rhIL-4 reduced the subsequent tumour necrosis factor alpha (TNF alpha) stimulation of prostaglandin E (PGE) and matrix metalloproteinase-3 (MMP-3) production by RSF. Thus, the potential anti-synovial monokine properties of rhIL-4 are not confined to inhibiting monokine production but also include the ability to interfere with their action on cells that constitute a substantial proportion of the rheumatoid synovium.


Asunto(s)
Antígenos CD , Artritis Reumatoide/inmunología , Interleucina-4/farmacología , Receptores del Factor de Necrosis Tumoral/efectos de los fármacos , Membrana Sinovial/inmunología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Alcaloides/farmacología , Unión Competitiva/efectos de los fármacos , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Fibroblastos/inmunología , Humanos , Interleucina-4/inmunología , Monocinas/biosíntesis , Monocinas/efectos de los fármacos , Proteína Quinasa C/antagonistas & inhibidores , Receptores Tipo I de Factores de Necrosis Tumoral , Proteínas Recombinantes/farmacología , Estaurosporina , Factor de Necrosis Tumoral alfa/biosíntesis
19.
Immunology ; 80(3): 367-72, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8288313

RESUMEN

Supernatants from rat peritoneal macrophage cultures stimulated with bacterial products contain a M(r) 36,000 factor that protects immature cortical thymocytes from loss of viability over a 4-hr incubation period in vitro. This effect could not be produced with purified transforming growth factor-beta or recombinant interleukin-6 (IL-6). Further, the partially purified M(r) 36,000 fraction was inactive in bioassays for IL-1 and tumour necrosis factor. Maximal production of the factor occurred 2 hr after the addition of 20 micrograms/ml of lipopolysaccharide, as assessed by the titre resulting in 100% protection of thymocytes in a viability assay. The detection of protective activity within 5 min after addition of the stimulant could be attributed to the release of intracellular stores but protein synthesis was required to account for the increasing titre up to peak levels. The titre fell rapidly after 2 hr so that activity could not be detected at 4 hr. This profile of release was refractory to repeated stimulation with lipopolysaccharide. Conjoint addition of lipopolysaccharide and indomethacin, did, however, allow release in response to subsequent challenge. Related to this finding, prostaglandin E2 completely inhibited the release of protective activity.


Asunto(s)
Activación de Macrófagos/inmunología , Macrófagos Peritoneales/inmunología , Monocinas/biosíntesis , Acetilmuramil-Alanil-Isoglutamina/inmunología , Animales , Células Cultivadas , Relación Dosis-Respuesta Inmunológica , Cinética , Lipopolisacáridos/inmunología , Monocinas/efectos de los fármacos , Prostaglandinas/fisiología , Inhibidores de la Síntesis de la Proteína/farmacología , Ratas , Ratas Endogámicas WF
20.
Toxicol Appl Pharmacol ; 119(2): 306-9, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8480341

RESUMEN

Short-term exposure of humans and animals to ozone results in increased lung neutrophils; however, the mechanisms underlying this response are not completely understood. We examined the potential involvement of the neutrophil chemotactic factor, macrophage inflammatory protein 2 (MIP-2), in ozone-induced inflammation. Exposure-response relationships for ozone and MIP-2 expression were characterized by exposing C57B1/6 mice to 0.1-2 ppm ozone for 3 hr and determining lung levels of MIP-2 mRNA 6 hr after exposure. Temporal relationships between ozone and MIP-2 were determined by exposing mice (2 ppm ozone x 3 hr) and characterizing MIP-2 mRNA expression 0, 2, 6, and 24 hr after exposure. Neutrophils in lung lavage fluid were determined in both exposure-response and time course studies. Ozone concentrations > or = 1.0 ppm increased MIP-2 mRNA and this increase corresponded with recruitment of neutrophils. MIP-2 mRNA was increased immediately after ozone exposure and decreased to control levels by 24 hr. To examine the role of direct oxidant effects in ozone-induced MIP-2 expression, alveolar macrophages were exposed in vitro for 4 hr to 10(-10)-10(-5) M hydrogen peroxide and MIP-2 expression was characterized. MIP-2 mRNA levels in lung macrophages were increased by > or = 10(-9) M hydrogen peroxide. In summary, our findings suggest the chemotactic protein MIP-2 may be responsible, at least in part, for ozone-induced increases in lung neutrophils and indicate that direct exposure of alveolar macrophages to an oxidant is sufficient to induce MIP-2 expression.


Asunto(s)
Citocinas/efectos de los fármacos , Monocinas/efectos de los fármacos , Ozono/farmacología , Administración por Inhalación , Animales , Secuencia de Bases , Quimiocina CXCL2 , Citocinas/genética , Expresión Génica/efectos de los fármacos , Gliceraldehído-3-Fosfato Deshidrogenasas/efectos de los fármacos , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Peróxido de Hidrógeno/farmacología , Técnicas In Vitro , Macrófagos Alveolares/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Monocinas/genética , Ozono/administración & dosificación , Fragmentos de Péptidos/efectos de los fármacos , Fragmentos de Péptidos/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Ratas , Ratas Endogámicas F344
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