Interleukin-12 drives the Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa.
In this study we examined mechanisms that regulate T-helper lymphocyte 1 (Th1) commitment in Helicobacter pylori-infected human gastric mucosa. The levels of gamma interferon (IFN-gamma), interleukin-4 (IL-4), and IL-12 in total extracts of gastric biopsies taken from H. pylori-infected and uninfected patients were determined by an enzyme-linked immunosorbent assay. The levels of signal transducer and activator of transcription 4 (STAT4), STAT6, and T-box expressed in T cells (T-bet) in total proteins extracted from gastric biopsies were determined by Western blotting. Finally, the effect of a neutralizing IL-12 antibody on expression of Th1 transcription factors and the levels of IFN-gamma in organ cultures of H. pylori-infected biopsies was examined. Increased levels of IFN-gamma and IL-12 were found in gastric biopsy samples of H. pylori-infected patients compared to the levels in uninfected patients. In addition, H. pylori-infected biopsies exhibited high levels of expression of phosphorylated STAT4 and T-bet. Higher levels of IFN-gamma and expression of Th1 transcription factors were associated with greater infiltration of mononuclear cells in the gastric mucosa. By contrast, production of IL-4 and expression of phosphorylated STAT6 were not associated with the intensity of mononuclear cell infiltration. In ex vivo organ cultures of H. pylori-infected biopsies, neutralization of endogenous IL-12 down-regulated the expression of phosphorylated STAT4 and T-bet and reduced IFN-gamma production. Our data indicated that IL-12 contributes to the Th1 cell commitment in H. pylori-infected human gastric mucosa.
Pellicanò
Antonia
A
Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro Magna Graecia, Campus Universitario di Germaneto, Viale Europa, 88100 Catanzaro, Italy.
Sebkova
Ladislava
L
Monteleone
Giovanni
G
Guarnieri
Giovanni
G
Imeneo
Maria
M
Pallone
Francesco
F
Luzza
Francesco
F
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D001706:Biopsy; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D050797:STAT4 Transcription Factor / Q000032:analysis; D050800:STAT6 Transcription Factor / Q000032:analysis; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000032:analysis; D000098815:T-bet Transcription Factor
D000906:Antibodies; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma