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-κB
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-κB
复制标题
DOI：
10.1074/jbc.m006883200
复制
发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
Gray-Owen, SD
中科院分区：
文献类型：
--
作者：
Muenzner, P;Naumann, M;Gray-Owen, SD
淋病奈瑟菌表达不透明相关（Opa）蛋白粘附素，介导与癌胚抗原相关细胞粘附分子（CEACAM;以前称为CD 66）受体家族的各种成员结合。虽然人脐静脉内皮细胞在体外表达很少的CEACAM受体，我们发现奈瑟菌感染诱导CEACAM 1，CEACAM 1 -3L和CECAM 1 -4L剪接变体的表达。这介导这些细胞对淋球菌的Opa（52）依赖性结合增加。诱导的受体表达不需要细菌Opa表达，但粘附细菌更快。由于诱导的时间过程与诱导的促炎细胞因子相似，我们测试了CEACAM 1表达是否可以通过类似的机制控制。淋球菌感染激活了由p50和p65组成的核因子-κ B（NF-κ B）异源二聚体，阻止激活的NF-κ B复合物核转位的抑制剂抑制CEACAM 1转录物表达。这些效应中的每一种都可以通过使用培养物或纯化的脂多糖代替完整的细菌来模拟。总之，我们的结果支持了一个模型，即外膜“水泡”，主动释放的淋球菌触发Toll样受体-4-依赖性激活NF-κ B，上调CEACAM 1的表达，使Opa（52）介导的奈瑟球菌结合。MF-kappaB对CEACAM 1表达的调节也意味着该受体在对感染的一般炎症反应中具有更广泛的作用。
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 MF-kappaB also implies a broader role for this receptor in the general inflammatory response to infection.