There are several aspects that might explain third these disconcordant results. In AGS cells, both the intracellular and secreted proportion of Progra nulin was separately analyzed. Since in ex vivo analysis, both compartments can not be differentiated, the increased Progranulin levels in antral mucosa might reflect both increased secretion and changes in epithelial Progranulin expression. Second, ex vivo analysis is per formed on complex samples including epithelial and immune cells, whereas the in vitro model only mirrors the direct interaction of H. pylori to epithelial derived AGS cells. Third, analyzing the Progranulin expression after 24 hours represents the effects of an acute infec tion, whereas changes in mucosal biopsies can be con sidered as long term effects of an chronic infection that are in a steady state.

Despite these limitations, data from the in vitro model allow the conclusion that a down regulation of epithelial SLPI expression does not affect the expression of Progranulin in AGS cells. Owing to the low molecular weight of granulins, no method is currently suitable to analyze quantitatively the levels of the Progranulin derived degradation products. Therefore, no statement can be made concerning the equilibrium between Pro granulin and granulins in gastric mucosa that might hypothetically be shifted towards granulins even the Progranulin levels are upregulated. Furthermore, it is of note that SLPI is not the only serine protease inhibitor expressed in the gastric mucosa. Recently, we identified elevated alpha 1 protease inhibitor levels in the mucosa of H.

pylori infected individuals. Since A1 PI can inhibit elastase to a similar extent as SLPI, a com pensatory mechanism is another potential explanation, while Progranulin is elevated, although SLPI levels are strongly diminished in relation to H. pylori infection. The observed association of induced Progranulin levels in context to H. pylori infection and its associated gastritis does not allow functional conclusions whether the upregu lation has an active regulatory role for the inflammatory process, or it merely reflects the inflammatory conditions of the underlying gastritis. Keeping in mind that Progranu lin acts as epithelial growth factor in other diseases, it is tempting to speculate that the upregulation of Progra nulin in H.

pylori associated gastritis might be involved in mucosal healing of gastric erosions ulcers induced by this infection. But at this moment, Cilengitide this remains purely specula tive since no functional data are available. Conclusions Taken together data from in vitro and ex vivo analysis, we can conclude that the proposed regulatory link between SLPI and Progranulin expression seems to be of no or low relevance in context to the H. pylori infec tion.