RESUMEN
The role of retinoblastoma protein-interacting zinc finger 1 (RIZ1) on the cell growth of mouse and human monocytic leukemia cells was examined. RIZ1 expression was induced in response to tumor necrosis factor (TNF)-α. The expression was dependent on the nuclear factor-κB and AKT signaling. Further, RIZ1 expression led to the augmentation of p53 expression and the silencing of RIZ1 prevented it. On the other hand, a p53 inhibitor enhanced the TNF-α-induced RIZ1 expression. Silencing of RIZ1 augmented the proliferative activity of TNF-α-treated cells. Therefore, it is suggested that RIZ1 negatively regulated the cell proliferation of monocytic leukemia cells via activation of p53.
Asunto(s)
Proteínas de Unión al ADN/farmacología , N-Metiltransferasa de Histona-Lisina/farmacología , Leucemia Mieloide/patología , Proteínas Nucleares/farmacología , Factores de Transcripción/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Animales , División Celular/efectos de los fármacos , Metilación de ADN , Cartilla de ADN , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , N-Metiltransferasa de Histona-Lisina/genética , Homeostasis , Humanos , Leucemia Mieloide/genética , Ratones , Neoplasias/genética , Neoplasias/patología , Proteínas Nucleares/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/genética , Transfección , Factor de Necrosis Tumoral alfa/genética , Proteína p53 Supresora de Tumor/efectos de los fármacosRESUMEN
Selective Alzheimer disease indicator-1 (seladin-1) is a broadly expressed oxidoreductase and is related to Alzheimer disease, cholesterol metabolism and carcinogenesis. The effect of lipopolysaccharide (LPS) on the expression of seladin-1 was examined using RAW 264.7 macrophage-like cells and murine peritoneal macrophages. Lipopolysaccharide induced the expression of seladin-1 protein and messenger RNA in those macrophages. The seladin-1 expression was also augmented by a series of Toll-like receptor ligands. The LPS augmented the expression of seladin-1 via reactive oxygen species generation and p38 activation. Seladin-1 inhibited LPS-induced activation of p38 but not nuclear factor-kappaB and inhibited the production of tumour necrosis factor-alpha in response to LPS. Moreover, seladin-1 inhibited LPS-induced osteoclast formation and enhanced LPS-induced alkaline phosphatase activity. Therefore, it was suggested that seladin-1 might be an LPS-responsible gene product and regulate the LPS-induced inflammatory response negatively.
Asunto(s)
Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Línea Celular , Lipopolisacáridos/inmunología , Macrófagos/inmunología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Ratones , Proteínas del Tejido Nervioso/efectos de los fármacos , Proteínas del Tejido Nervioso/genética , Osteoclastos/citología , Osteoclastos/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/efectos de los fármacos , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Reacción en Cadena de la Polimerasa , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/efectos de los fármacosRESUMEN
The effect of a series of toll-like receptor (TLR) ligands on the production of nitric oxide (NO) in mouse B1 cells was examined by using CD5(+) IgM(+) WEHI 231 cells. The stimulation with a series of TLR ligands, which were Pam3Csk4 for TLR1/2, poly I:C for TLR3, lipopolysaccharide (LPS) for TLR4, imiquimod for TLR7 and CpG DNA for TLR9, resulted in enhanced NO production via augmented expression of an inducible type of NO synthase (iNOS). LPS was most potent for the enhancement of NO production, followed by poly I:C and Pam3Csk4. Imiquimod and CpG DNA led to slight NO production. The LPS-induced NO production was dependent on MyD88-dependent pathway consisting of nuclear factor (NF)-kappaB and a series of mitogen-activated protein kinases (MAPKs). Further, it was also dependent on the MyD88-independent pathway consisting of toll-IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) and interferon regulatory factor (IRF)-3. Physiologic peritoneal B1 cells also produced NO via the iNOS expression in response to LPS. The immunological significance of TLR ligands-induced NO production in B1 cells is discussed.
Asunto(s)
Linfocitos B/inmunología , Óxido Nítrico/metabolismo , Receptores Toll-Like/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Aminoquinolinas/metabolismo , Animales , Antígenos CD5/metabolismo , Línea Celular , ADN/metabolismo , Femenino , Imiquimod , Inmunoglobulina M/metabolismo , Inductores de Interferón/metabolismo , Ligandos , Lipopolisacáridos/metabolismo , Ratones , Ratones Endogámicos BALB C , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nitritos/metabolismo , Oligodesoxirribonucleótidos/genética , Oligodesoxirribonucleótidos/metabolismo , Poli I-C/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Astrocyte elevated gene-1 (AEG-1) is induced by human immunodeficiency virus 1 (HIV-1) infection and involved in tumour progression, migration and invasion as a nuclear factor-kappaB (NF-kappaB) -dependent gene. The involvement of AEG-1 on lipopolysaccharide (LPS) -induced proinflammatory cytokine production was examined. AEG-1 was induced via NF-kappaB activation in LPS-stimulated U937 human promonocytic cells. AEG-1 induced by LPS subsequently regulated NF-kappaB activation. The prevention of AEG-1 expression inhibited LPS-induced tumour necrosis factor-alpha and prostaglandin E(2) production. The AEG-1 activation was not induced by toll-like receptor ligands other than LPS. Therefore, AEG-1 was suggested to be a LPS-responsive gene and involved in LPS-induced inflammatory response.
Asunto(s)
Moléculas de Adhesión Celular/biosíntesis , Lipopolisacáridos/inmunología , Monocitos/inmunología , Receptor Toll-Like 4/metabolismo , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Dinoprostona/biosíntesis , Dinoprostona/inmunología , Humanos , Proteínas de la Membrana , Monocitos/efectos de los fármacos , FN-kappa B/agonistas , FN-kappa B/metabolismo , Proteínas de Unión al ARN , Transducción de Señal , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
The effect of thalidomide on lipopolysaccharide-induced nitric oxide (NO) production was studied using RAW 264.7 macrophage-like cells. Thalidomide significantly inhibited lipopolysaccharide-induced NO production via reduced expression of an inducible NO synthase. Thalidomide reduced the phosphorylation of the p65 nuclear factor-kappaB subunit, inhibitory kappaB (IkappaB) and IkappaB kinase in lipopolysaccharide-stimulated cells. However, thalidomide did not affect the expression of interferon-beta (IFN-beta) and interferon regulatory factor-1 in response to lipopolysaccharide. Further, thalidomide inhibited the MyD88 augmentation in lipopolysaccharide-stimulated cells, whereas it did not alter the expression of TIR domain-containing adaptor-inducing IFN-beta in the MyD88-independent pathway. Thalidomide significantly inhibited the NO production in response to Pam(3)Cys, CpG DNA and imiquimod as MyD88-dependent Toll-like receptor (TLR) ligands, but not polyI:C as a MyD88-independent TLR ligand. Therefore, thalidomide was suggested to inhibit lipopolysaccharide-induced NO production via downregulation of the MyD88-dependent signal pathway. The anti-inflammatory action of thalidomide might be involved in the prevention of lipopolysaccharide-mediated lethality in mice.
Asunto(s)
Inmunosupresores/farmacología , Lipopolisacáridos/inmunología , Óxido Nítrico/antagonistas & inhibidores , Talidomida/farmacología , Animales , Línea Celular , Supervivencia Celular , Regulación hacia Abajo , Quinasa I-kappa B/metabolismo , Proteínas I-kappa B/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fosforilación , Análisis de Supervivencia , Factor de Transcripción ReIA/metabolismoRESUMEN
The effect of thalidomide on epidermal growth factor (EGF)-induced cell growth was examined. Thalidomide inhibited EGF-induced cell growth in mouse and human monocytic leukemia cells, RAW 264.7, U937 and THP-1. Thalidomide inhibited EGF-induced phosphorylation of extracellular signal regulated kinase (ERK) 1/2, but not p38 and stress-activated protein kinase (SAPK)/JNK. The phosphorylation of MEK1/2 and Raf at Ser 338 as the upstream molecules of ERK 1/2 was also prevented by thalidomide. Further, it inhibited EGF-induced Ras activation through preventing the transition to GTP-bound active Ras. Thalidomide inhibited the Ras activation induced by lipopolysaccharide (LPS) and vascular endothelial growth factor (VEGF) as well as EGF. There was no significant difference in the expression and function of EGF receptor between thalidomide-treated and non-treated cells. Therefore, thalidomide was suggested to inhibit EGF-induced cell growth via inactivation of Ras.