In this study we examined mechanisms that regulate T-helper lymphocyte I (Th1) commitment in Helico-bacter 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.

Pellicano, A., Sebkova, L., Monteleone, G., Guarnieri, G., Imeneo, M., Pallone, F., et al. (2007). Interleukin-12 drives the Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa. INFECTION AND IMMUNITY, 75(4), 1738-1744 [10.1128/IAI.01446-06].

Interleukin-12 drives the Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa

MONTELEONE, GIOVANNI;PALLONE, FRANCESCO;
2007-01-01

Abstract

In this study we examined mechanisms that regulate T-helper lymphocyte I (Th1) commitment in Helico-bacter 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.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - GASTROENTEROLOGIA
English
gamma interferon; interleukin 12; interleukin 4; STAT4 protein; STAT6 protein; transcription factor; transcription factor TBX5; adult; aged; article; biopsy technique; cell infiltration; clinical article; controlled study; cytokine production; enzyme linked immunosorbent assay; ex vivo study; female; Helicobacter pylori; human; male; mononuclear cell; organ culture; priority journal; protein expression; stomach biopsy; stomach mucosa; Th1 cell; Adult; Aged; Antibodies; Biopsy; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interferon Type II; Interleukin-12; Interleukin-4; Male; Middle Aged; Organ Culture Techniques; Signal Transduction; STAT4 Transcription Factor; STAT6 Transcription Factor; T-Box Domain Proteins
Pellicano, A., Sebkova, L., Monteleone, G., Guarnieri, G., Imeneo, M., Pallone, F., et al. (2007). Interleukin-12 drives the Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa. INFECTION AND IMMUNITY, 75(4), 1738-1744 [10.1128/IAI.01446-06].
Pellicano, A; Sebkova, L; Monteleone, G; Guarnieri, G; Imeneo, M; Pallone, F; Luzza, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/28547
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