Role of activated protein C in Helicobacter pylori-associated gastritis

The protein C (PC) pathway has recently been suggested to play a role in th e regulation of the inflammatory response. To further extend the anti-infla mmatory effect of activated PC (APC) in vivo, particularly its biological r elevance to human disease, the activity of APC in the mucosa of patients wi th Helicobacter pylori-associated gastritis and the effect of vacuolating c ytotoxin (VacA), cytotoxin-associated antigen (CagA), and H. pylori lipopol ysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis, There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex w ere measured by immunoassays. The level of PC was significantly decreased a nd the level of APC-PCI complex was significantly increased in biopsy speci mens from gastric corpus and antrum in patients with H. pylori-associated g astritis as compared to H. pylori-negative subjects. The concentrations of VacA CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-alpha) induced by H. pylori LPS. Overall, these results s uggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-alpha secreti on may serve to protect H. pylori-induced gastric mucosal damage.