RRC ID 42473
Author Nakamura M, Gabazza EC, Imoto I, Yano Y, Taguchi O, Horiki N, Fukudome K, Suzuki K, Adachi Y.
Title Anti-inflammatory effect of activated protein C in gastric epithelial cells.
Journal J. Thromb. Haemost.
Abstract It has been previously demonstrated that activated protein C (APC) plays an important role in the inhibition of inflammation in the gastric mucosa from patients with Helicobacter pylori infection. However, the role of gastric epithelial cells in the anti-inflammatory activity of APC remains unknown. In the present study, we evaluated the anti-inflammatory activity of APC and the expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) in gastric epithelial cells. The gastric epithelial cell lines, MKN-1 and AGS, and gastric biopsy samples from patients with and without H. pylori infection were used in the experiments. Polymerase chain reaction showed that gastric epithelial cell lines express EPCR and TM. Flow cytometry analysis also showed EPCR expression in both cells. H. pylori infection significantly increased EPCR expression compared with non-infected cells. Similar results were observed in vivo when samples from patients with and without H. pylori infection were analyzed for EPCR protein expression. Significant TM activity was found on AGS and MKN-1 cells stimulated with LPS from Escherichia coli and VacA antigen. APC was able to significantly inhibit the secretion of MCP-1 and IL-1beta induced by H. pylori homogenate in AGS cells. APC also remarkably suppressed the mRNA expression and secretion of MCP-1 from AGS cells infected with H. pylori. These results demonstrated the expression of components of the protein C pathway on gastric epithelial cells and that APC may play a critical role in the protection against gastric mucosal inflammation.
Volume 3(12)
Pages 2721-9
Published 2005-12
DOI 10.1111/j.1538-7836.2005.01635.x
PMID 16246255
MeSH Antigens / analysis Antigens / genetics Antigens / physiology Antigens, CD Blood Coagulation Factors / analysis Blood Coagulation Factors / genetics Blood Coagulation Factors / physiology Cells, Cultured Cytokines / metabolism Endothelial Protein C Receptor Endothelium, Vascular / cytology Epithelial Cells / chemistry* Epithelial Cells / metabolism Glycoproteins / analysis Glycoproteins / genetics Glycoproteins / physiology Helicobacter Infections / metabolism Helicobacter Infections / pathology Humans Inflammation / pathology* Protein C / metabolism Protein C / physiology* RNA, Messenger / analysis Receptor, PAR-1 / physiology Receptors, Cell Surface / analysis Receptors, Cell Surface / genetics Receptors, Cell Surface / physiology Stomach / cytology* Stomach / pathology Thrombomodulin / analysis Thrombomodulin / genetics Thrombomodulin / metabolism
IF 4.662
Times Cited 9
Human and Animal Cells