RESUMEN
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.