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Regulation of Endotoxin - Induced TNF-alpha Gene Expression
Journal of the Korean Society for Microbiology ; : 71-80, 1997.
Artigo em Coreano | WPRIM | ID: wpr-211416
ABSTRACT
It is well known that tumor necrosis factor (TNF-a), interleukin-1, platelet-activating factor (PAF) and arachidonic acid metabolites, such as thromboxane and leukotriens, are major mediators involved in the pathogenesis of endotoxic shock. In this study, we have investigated the effect of pentoxifylline (inhibitor of TNF-a release), BN50739 (PAF antagonist), indomethacin (cyclooxygenase inhibitor) and diethylcarbamazine (lipoxygenase inhibitor) on LPS- induced lethality as well as the relationship between major mediators in endotoxic shock. All inhibitors described above except diethylcarbamazine significantly protected mice against LPS- induced lethality. BN50739 and indomethacin were also effective in protection of TNF-a-induced lethality. The elevation of circulating TNF-a by LPS was significantly blocked by BN50739, but not affected by indomethacin. Convulsion appeared shortly after LPS injection was prevented by BN50739 but not by indomethacin, whereas diarrhea and limited movement was prevented by indomethacin but not by BN50739. These results indicate that i) TNF-a, PAF and cyclooxygenase products are important mediators involved in the pathogenesis of septic shock and ii) TNF-a directly influenced the release or production of PAF as well as cyclooxygenase products, and strongly suggest that i) TNF-a and PAF stimulate the release of each other via positive feedback network but TNF-a and cyclooxygenase products do not form the network and ii) PAF and cyclooxygenase product appear not to affect the release of each other.
Assuntos
Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Pentoxifilina / Convulsões / Choque Séptico / Expressão Gênica / Indometacina / Interleucina-1 / Fator de Necrose Tumoral alfa / Ácido Araquidônico / Prostaglandina-Endoperóxido Sintases / Diarreia Limite: Animais Idioma: Coreano Revista: Journal of the Korean Society for Microbiology Ano de publicação: 1997 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Pentoxifilina / Convulsões / Choque Séptico / Expressão Gênica / Indometacina / Interleucina-1 / Fator de Necrose Tumoral alfa / Ácido Araquidônico / Prostaglandina-Endoperóxido Sintases / Diarreia Limite: Animais Idioma: Coreano Revista: Journal of the Korean Society for Microbiology Ano de publicação: 1997 Tipo de documento: Artigo