ROLE OF ADHERENCE IN INTERLEUKIN-8 INDUCTION IN HELICOBACTER-PYLORI-ASSOCIATED GASTRITIS

Active Helicobacter pylori-associated gastritis is characterized by a dense mucosal infiltration with granulocytes, Since H, pylori is nonin vasive, secondary signals must induce the accumulation of granulocytes . Interleukin-8 (IL-8) has been shown to play a key role in this event , Using competitive reverse transcriptase-PCR on mRNA from gastric bio psies, we could show a clear correlation between the amount of IL-8 tr anscripts and the activity of H, py[ori gastritis, Due to the inabilit y of the bacterium to invade host cells, the epithelial layer is a pot ential candidate as an IL-8 source, To study the mechanism of IL-8 ind uction, established gastric carcinoma epithelial cell lines (AGS and K ato III) and well-defined H, pylori strains were used in a modified in vitro system, The experimental design enabled us to prevent direct co ntact of bacteria with epithelial cells by use of a filter membrane wh ich did not block secreted bacterial products crossing the membrane, T he data clearly showed that the direct contact of the bacterial cell w ith the epithelial cell is necessary for optimal IL-8 production becau se not only live bacteria, but also metabolically inactive bacteria, i ncreased IL-8 secretion, Neither purified lipopolysaccharide nor water -soluble protein fractions of H. pylori NCTC 11637 and Tx30a nor the c ytotoxin of H. pylori was able to increase IL-8 production significant ly by the epithelial cells used, Furthermore, preparations of total me mbrane and outer membrane proteins of N. pylori were not able to stimu late IL-8 release in vitro, Accumulatively, these results imply that a ctive metabolism is not necessary for stimulation as long as there is an intact membrane aiding the presentation of a stimulating membrane c omplex or aggregate on the surface of the bacteria, From these results , we conclude that whole bacteria and their direct contact with epithe lial cells may be critical for IL-8 induction in vivo.