Human gastric epithelium produces IL-4 and IL-4delta2 isoform only upon Helicobacter pylori infection.
Recent evidence suggests that interleukin-4 (IL-4) is related to mucosal tolerance by which an injurious immune response is prevented, suppressed or shifted to a non-injurious response. We investigated the expression of IL-4 and its splice variant isoform IL-4delta2 in gastric epithelial cells of healthy subjects and gastritis patients infected with Helicobacter pylori (H. pylori) with or without the cag pathogenicity island (cag-PAI). IL-4 and IL-4delta2 mRNAs were evaluated in microdissected gastric epithelium and in AGS cell lines co-cultured with H. pylori B128 or SS1 strains. IL-4 mRNA was consistently detected in microdissected gastric epithelial cells from healthy subjects. The IL-4 mRNA expression was low in H. pylori?infected patients, and markedly reduced in cag-PAI-positive ones. IL-4delta2 mRNA was expressed on gastric epithelium of H. pylori-infected patients, but not in healthy subjects. The IL-4delta2 expression was lower in cag-PAI-positive than in cag-PAI-negative H. pylori infected patients. AGS cells also produced IL-4 mRNA upon SS1 strain stimulation, whereas IL-4delta2 mRNA expression was detected in AGS co-cultured with either SS1 or B128 strains. An inverse correlation was documented between IL-4 and IL-4delta2 mRNA expression by microdissected gastric epithelial cells and the score of gastritis. IL-4, but not IL-4delta2, is expressed by gastric epithelium of healthy subjects, whereas IL-4delta2 and lesser IL-4 mRNA are detectable in the gastric epithelium of H. pylori-infected patients. Data suggest that gastric epithelial cells might regulate the balance between tolerance and immune response by the fine tuning of IL-4 and IL-4delta2 expression.
Orsini
B
B
Department of Clinical Pathophysiology, Gastroenterology Unit, University of Florence, Italy. b.orsini@dfc.unifi.it
Vivas
J R
JR
Ottanelli
B
B
Amedei
A
A
Surrenti
E
E
Galli
A
A
Milani
S
S
Pinzani
P
P
Del Prete
G
G
Surrenti
C
C
Baldari
C T
CT
Touati
E
E
D' Elios
M M
MM
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D045744:Cell Line, Tumor; D002469:Cell Separation; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D044404:Genomic Islands / Q000235:genetics; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D042282:Microdissection; D011706:Pyloric Antrum; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D015847:Interleukin-4; D012313:RNA