Interleukin 12 Drives Th1 Signaling Pathway in Helicobacter Pylori-infected Human Gastric Mucosa

This study examines mechanisms that regulate T helper lymphocyte (Th) 1 commitment in Helicobacter pylori-infected human gastric mucosa. Interferon (IFN)-γ, interleukin (IL)-4, and IL-12 were measured in total extracts of gastric biopsies taken from H. pylori-infected and uninfected patients by enzyme linked immunosorbent assay. STAT4, STAT6, and Tbet were examined in total proteins extracted from gastric biopsies by Western blotting. Finally, the effect of a neutralizing IL-12 antibody on the expression of Th1 transcription factors and levels of IFN-γ was examined in organ cultures of H. pylori-infected biopsies. Increased levels of IFN-γ and IL-12 were found in gastric biopsy samples of H. pyloriinfected patients compared to uninfected patients. Accordingly, H. pylori-infected biopsies exhibited high expression of phosphorylated STAT4 and T-bet. Higher levels of IFN-γ and expression of Th1 transcription factors were associated with higher 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 p-Stat4 and T-bet and reduced IFN-γ production. Data indicate that IL-12 contributes to the Th1 cell commitment in H. pylori-infected human gastric mucosa. AC CE PT ED on A uust 9, 2017 by gest http/iai.asm .rg/ D ow nladed fom