Proteolysis of ICAM-1 on human oral epithelial cells by gingipains.
Cysteine proteinases (gingipains) from Porphyromonas gingivalis are considered key virulence factors of severe periodontitis and host immune evasion. Since expression of intercellular adhesion molecule-1 (ICAM-1) on gingival epithelium is indispensable in polymorphonuclear leukocyte (PMN) migration at the site of periodontitis, we examined the effects of gingipains on the expression of ICAM-1 on human oral epithelial cell lines (KB and HSC-2) by flow cytometry and Western blotting. We found that three purified forms of gingipains efficiently reduced ICAM-1 expression on the cells in a time- and dose-dependent manner. Gingipains reduced the expression on fixed cells and degraded the ICAM-1 in the cell membranes, indicating that the reduction resulted from direct proteolysis. They then disturbed the ICAM-1-dependent adhesion of PMNs to the cells. These results indicate that gingipains cleave ICAM-1 on oral epithelial cells, consequently disrupting PMN-oral epithelial cell interaction, and are involved in immune evasion by the bacterium in periodontal tissues.
D018829:Adhesins, Bacterial / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects*; D007624:KB Cells; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects; D016966:Porphyromonas gingivalis / Q000201:enzymology; D013997:Time Factors
D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D018799:Intercellular Adhesion Molecule-1; D003546:Cysteine Endopeptidases