Escherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells
Hyperactivation of systemic renin-angiotensin system (RAS) during sepsis is well documented. However, the behavior of intrarenal RAS in the context of endotoxemia is yet to be defined. the present study evaluates the direct effect of Escherichia coli lipopolysaccharide (LPS) on immortalized human me...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2006 |
| País: | Brasil |
| Institución: | Universidade Federal de São Paulo (UNIFESP) |
| Repositorio: | Repositório Institucional da UNIFESP |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unifesp.br:11600/28754 |
| Acceso en línea: | http://dx.doi.org/10.1038/sj.ki.5000134 http://repositorio.unifesp.br/handle/11600/28754 |
| Access Level: | acceso abierto |
| Palabra clave: | mesangial cell lipopolysaccharide renin-angiotensin system acute renal failure sepsis |
| Sumario: | Hyperactivation of systemic renin-angiotensin system (RAS) during sepsis is well documented. However, the behavior of intrarenal RAS in the context of endotoxemia is yet to be defined. the present study evaluates the direct effect of Escherichia coli lipopolysaccharide (LPS) on immortalized human mesangial cell (HMC) RAS. Quiescent HMC were incubated with vehicle or LPS (1-100 mu g/ml), and levels of angiotensin I and II (Ang I and II) and their metabolites were analyzed by high-performance liquid chromatography. in addition, angiotensin-converting enzyme (ACE) and renin activity were also investigated. Cell lysate and extracellular medium levels of Ang II were rapidly reduced (1 h) in a time- and concentration-dependent manner, reaching a significant -9 fold-change (P < 0.001) after 3 h of LPS incubation. Similar results were obtained for Ang I levels (-3 fold-change, P < 0.001). We ruled out Ang I and II degradation, as levels of their metabolic fragments were also significantly decreased by LPS. ACE activity was slightly increased following LPS incubation. On the other hand, renin activity was significantly inhibited, as Ang I concentration elevation following exogenous angiotensinogen administration was blunted by LPS (-60% vs vehicle, P < 0.001). Renin and angiotensinogen protein levels were not affected by LPS according to Western blot analysis. Taken together, these data demonstrate for the first time that LPS significantly downregulates HMC RAS through inhibition of renin or renin-like activity. These findings are potentially related to the development of and/or recovery from acute renal failure in the context of sepsis. |
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