Pathogenic Neisseria trigger expression of their carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1; previously CD66a) receptor on primary endothelial cells by activating the immediate early response transcription factor, nuclear factor-kappaB.
J Biol Chem
; 276(26): 24331-40, 2001 Jun 29.
Article
en En
| MEDLINE
| ID: mdl-11306560
ABSTRACT
Neisseria gonorrhoeae express opacity-associated (Opa) protein adhesins that mediate binding to various members of the carcinoembryonic antigen-related cellular adhesion molecule (CEACAM; previously CD66) receptor family. Although human umbilical vein endothelial cells express little CEACAM receptor in vitro, we found neisserial infection to induce expression of CEACAM1, CEACAM1-3L, and CECAM1-4L splice variants. This mediates an increased Opa(52)-dependent binding of gonococci by these cells. The induced receptor expression did not require bacterial Opa expression, but it was more rapid with adherent bacteria. Because the time course of induction was similar to that seen for induced proinflammatory cytokines, we tested whether CEACAM1 expression could be controlled by a similar mechanism. Gonococcal infection activated a nuclear factor-kappaB (NF-kappaB) heterodimer consisting of p50 and p65, and inhibitors that prevent the nuclear translocation of activated NF-kappaB complex inhibited CEACAM1 transcript expression. Each of these effects could be mimicked by using culture filtrates or purified lipopolysaccharide instead of intact bacteria. Together, our results support a model whereby the outer membrane "blebs" that are actively released by gonococci trigger a Toll-like receptor-4-dependent activation of NF-kappaB, which up-regulates the expression of CEACAM1 to allow Opa(52)-mediated neisserial binding. The regulation of CEACAM1 expression by NF-kappaB also implies a broader role for this receptor in the general inflammatory response to infection.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adhesión Bacteriana
/
Endotelio Vascular
/
Antígenos de Diferenciación
/
Antígenos CD
/
FN-kappa B
/
Proteínas de Drosophila
/
Neisseria gonorrhoeae
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2001
Tipo del documento:
Article
País de afiliación:
Alemania