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.
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<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.
Wex
Thomas
T
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany. thomas.wex@medizin.uni-magdeburg.de
Treiber
Gerhard
G
Venerito
Marino
M
Leodolter
Andreas
A
Peitz
Ulrich
U
Kuester
Doerthe
D
Hritz
Istvan
I
Krueger
Sabine
S
Roessner
Albert
A
Malfertheiner
Peter
P
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism*; D016480:Helicobacter pylori / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor; D013270:Stomach / Q000166:cytology / Q000382:microbiology; D013274:Stomach Neoplasms / Q000378:metabolism
D017931:DNA Primers; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor