Down-regulation of secretory leukocyte protease inhibitor expression in gastric mucosa is a general phenomenon in Helicobacter pylori-related gastroduodenal diseases.
BACKGROUND
Secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein of the gastric mucosa exerting anti-microbial and anti-inflammatory effects. Recently, a local down-regulation of antral SLPI expression in Helicobacter pylori (Hp)-infected healthy volunteers was demonstrated.


OBJECTIVE
To analyze mucosal SLPI expression in patients with various gastroduodenal disorders.


METHODS
The prospective study included 90 patients with following gastroduodenal disorders diagnosed: gastric cancer (GC, n=22), duodenal ulcer (DU, n=17), Hp-positive dyspeptic patients (NUD, n=31) and Hp-negative NUD (n=20). During esophagogastroduodenoscopy, biopsies were taken each from antrum, corpus and tumor. SLPI expression was analyzed by quantitative RT-PCR and ELISA.


RESULTS
Antral SLPI levels were reduced in all Hp-infected patients (NUD, DU, GC) by about 75% (1,494-1,826 pg/50 microg protein) compared to Hp-negative NUD (6,563 pg/50 microg protein, p<0.001, ANOVA). Tumor tissue had twofold higher SLPI levels than surrounding tumor-free gastric mucosa (3,900 vs. 1,826 pg/50 microg protein, p=0.013), but revealed reduced SLPI levels compared to Hp-negative NUD patients (p=0.067). No differences were found between SLPI expression of intestinal and diffuse GC. SLPI transcript levels were unchanged throughout all groups and locations implying that transcriptional regulation of SLPI is not involved.


CONCLUSIONS
Local down-regulation of SLPI in antral mucosa is a general phenomenon of Hp-related diseases.
Wex
Thomas
T
Clinic for Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany. thomas.wex@medizin.uni-magdeburg.de
Sokic-Milutinovic
Aleksandra
A
Todorovic
Vera
V
Bjelovic
Milos
M
Milosavljevic
Tomica
T
Pesko
Predrag
P
Malfertheiner
Peter
P
D000907:Antibodies, Bacterial / Q000032:analysis; D001706:Biopsy; D015536:Down-Regulation / Q000235:genetics*; D016145:Endoscopy, Digestive System; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D005756:Gastritis / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology*; D005819:Genetic Markers; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology*
D000907:Antibodies, Bacterial; D005819:Genetic Markers; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D012313:RNA