NF-kappaB translocation and endothelial cell activation is potentiated by macrophage-released signals co-secreted with TNF-alpha and IL-1beta.
Inflamm Res
; 53(10): 567-75, 2004 Oct.
Article
en En
| MEDLINE
| ID: mdl-15597152
ABSTRACT
OBJECTIVE AND METHODS:
Over-expression of the immune response can lead to pathological conditions such as septic shock or chronic inflammation. Endothelial cell activation by pro-inflammatory products of activated macrophages plays a key role in these conditions. Here we examine the response of primary human endothelial cells (HUVEC) to conditioned media (CM) obtained from LPS-activated macrophages. We further characterized the translocation of NF-kappaB in the presence of CM by studying the degradation rate of individual IkappaB isoforms.RESULTS:
We show that, as expected, CM induced NF-kappaB translocation, as well as adhesion capacity in HUVEC. We further show that this response is critically dependent on TNF-alpha and IL1beta naturally present in the CM. However, both the amplitude of NF-kappaB translocation and adhesiveness observed with CM were well beyond the saturation levels attained after the sole stimulation with recombinant TNF-alpha and IL-1beta, either separately or together. Our results show that CM induced a faster degradation of the IkappaB-beta and IkappaB-epsilon isoforms than the recombinant cytokines, leading to an enhanced recruitment of NF-kappaB activity.CONCLUSIONS:
The above results suggest that the physiological context of factors co-secreted by LPS-activated macrophages enhances TNF-alpha mediated endothelial activation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Endotelio Vascular
/
FN-kappa B
/
Interleucina-1
/
Factor de Necrosis Tumoral alfa
/
Células Endoteliales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Inflamm Res
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Año:
2004
Tipo del documento:
Article