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-kappa B

Neisseria gonorrhoeae express opacity-associated (Opa) protein adhesins tha t mediate binding to various members of the carcinoembryonic antigen-relate d cellular adhesion molecule (CEACAM; previously CD66) receptor family. Alt hough human umbilical vein endothelial cells express little CEACAM receptor in vitro, we found neisserial infection to induce expression of CEACAM1, C EACAM1-3L, and CECAM1-4L splice variants. This mediates an increased Opa(52 )-dependent binding of gonococci by these cells. The induced receptor expre ssion 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 expr ession could be controlled by a similar mechanism. Gonococcal infection act ivated a nuclear factor-kappaB (NF-kappaB) heterodimer consisting of p50 an d p65, and inhibitors that prevent the nuclear translocation of activated N F-kappaB complex inhibited CEACAM1 transcript expression. Each of these eff ects could be mimicked by using culture filtrates or purified lipopolysacch aride instead of intact bacteria. Together, our results support a model whe reby the outer membrane "blebs" that are actively released by gonococci tri gger a Toll-like receptor-4-dependent activation of NF-kappaB, which up-reg ulates the expression of CEACAM1 to allow Opa(52)-mediated neisserial bindi ng. The regulation of CEACAM1 expression by MF-kappaB also implies a broade r role for this receptor in the general inflammatory response to infection.