Department of Genetics, Microbiology, and Toxicology, Stockholm University, Stockholm, Sweden.
PLoS One. 2011 Jan 27;6(1):e16369. doi: 10.1371/journal.pone.0016369.
Adhesion of the human pathogen Neisseria gonorrhoeae has established effects on the host cell and evokes a variety of cellular events including growth factor activation. In the present study we report that infection with N. gonorrhoeae causes altered amphiregulin processing and release in human epithelial cells. Amphiregulin is a well-studied growth factor with functions in various cell processes and is upregulated in different forms cancer and proliferative diseases. The protein is prototypically cleaved on the cell surface in response to external stimuli. We demonstrate that upon infection, a massive upregulation of amphiregulin mRNA is seen. The protein changes its subcellular distribution and is also alternatively cleaved at the plasma membrane, which results in augmented release of an infection-specific 36 kDa amphiregulin product from the surface of human cervical epithelial cells. Further, using antibodies directed against different domains of the protein we could determine the impact of infection on pro-peptide processing. In summary, we present data showing that the infection of N. gonorrhoeae causes an alternative amphiregulin processing, subcellular distribution and release in human epithelial cervical cells that likely contribute to the predisposition cellular abnormalities and anti-apoptotic features of N. gonorrhoeae infections.
人类病原体淋病奈瑟菌的黏附已对宿主细胞产生既定影响，并引发多种细胞事件，包括生长因子激活。在本研究中，我们报告淋病奈瑟菌感染可导致人上皮细胞中变形的 Amphiregulin 加工和释放。Amphiregulin 是一种研究充分的生长因子，在多种细胞过程中发挥作用，并在上皮细胞癌和增殖性疾病中以上调的形式存在。该蛋白在细胞表面受到外部刺激时被典型地切割。我们证明，感染后， Amphiregulin mRNA 大量上调。该蛋白改变其亚细胞分布，也在质膜处被替代切割，这导致从人宫颈上皮细胞表面释放出一种感染特异性的 36 kDa Amphiregulin 产物。此外，我们使用针对该蛋白不同结构域的抗体，可确定感染对前肽加工的影响。总之，我们提供的数据表明，淋病奈瑟菌的感染可导致人宫颈上皮细胞中 Amphiregulin 的替代加工、亚细胞分布和释放，这可能有助于淋病奈瑟菌感染的细胞异常和抗凋亡特征的倾向性。
