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The secretory leukocyte protease inhibitor (SLPI) exerts antiproteolytic activity towards serine proteases, as well as anti-microbial and anti-inflammatory effects. To investigate its role in  H. pylori -mediated diseases, SLPI expression was analyzed by RT-PCR, ELISA and immunohistochemistry in clinical samples and gastric tumor cell lines. Determination of the mucosal SLPI levels in 126 patients confirmed the previously reported downregulation of SLPI in  H. pylori -infected patients. The lower SLPI levels in antral biopsies of  H. pylori -positive subjects were associated with a 30-fold increase ( p &lt;0.01) in neutrophil elastase activity, and a significant negative correlation was demonstrated for both parameters (R=-0.63,  p =0.0002). Eradication of the bacterium in a long-term study (5–7 years) led to a recovery of mucosal SLPI expression.  In vitro  experiments using four gastric tumor cell lines (AGS, MKN-28, MKN-45, NCI-N87) generally confirmed the clinical findings. While the co-incubation of these cell lines with  H. pylori  resulted in lower or unchanged SLPI protein levels, the corresponding SLPI mRNA amounts were upregulated by up to five-fold ( p =0.006) in all cell lines. Taken together, these results indicate that the reduction in antral SLPI levels in  H. pylori -infected subjects has a functional relevance for gastric mucosa and the  H. pylori -induced decrease in SLPI is primarily regulated at the posttranslational level.

biological chemistry

Helicobacter pylori -induced downregulation of the secretory leukocyte protease inhibitor (SLPI) in gastric epithelial cell lines and its functional relevance for  H. pylori -mediated diseases