Effect of oral hepatocyte growth factor gene mediated by attenuated salmonella on 2-, 4-, 6-trinitro-benzene-sulfonic-acid-induced ulcerative colitis in rat

J Gastroenterol Hepatol. 2012 Mar;27(3):609-15. doi: 10.1111/j.1440-1746.2011.06894.x.

Abstract

Background and aim: In order to explore a new therapeutic method, we investigated the effects of exogenously expressed hepatocyte growth factor mediated by attenuated salmonella (TPH) on rats with ulcerative colitis (UC) induced by 2-, 4-, 6-trinitro-benzene-sulfonic acid.

Methods: The UC rats were treated with TPH, attenuated salmonella with a eukaryotic expression vector (TP) or sodium bicarbonate (model control [MC]) every other day. Cluster of differentiation (CD)4(+) and CD8(+) T cells and immunoglobulins in the blood were analyzed by flow cytometry. The HGF expression was determined by immunohistochemistry. A macroscopic-scale observation of the colon and a histological assessment were also carried out.

Results: The CD4(+) T counts and the CD4(+) /CD8(+) ratio in the TPH group were significantly lower than that in the MC group. The immunoglobulin M and immunoglobulin G(1) levels in the TPH group were significantly lower than that in the MC group and TP group. After treatment with TPH, the symptoms of the ulcerative rats were significantly alleviated. The colonic lesion grades in the TPH group were lower than that in the TP group and MC group. Significant improvement occurred after the TPH treatment, as evidenced by alleviated mucosal inflammation. At 7 days post-treatment, the HGF expression in the colonic tissues that were treated with TPH was stronger than that in the samples treated with TP.

Conclusions: TPH inhibits the proliferation of T lymphocytes and the antibody production of B lymphocytes. Furthermore, it ameliorates mucosal inflammation and promotes the regeneration of mucosa and the healing of the colonic ulceration.

MeSH terms

  • Animals
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology*
  • Female
  • Genetic Vectors
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Hepatocyte Growth Factor / therapeutic use*
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Male
  • Rats
  • Rats, Wistar
  • Salmonella typhimurium / genetics
  • Transformation, Bacterial
  • Trinitrobenzenesulfonic Acid

Substances

  • Immunoglobulin G
  • Immunoglobulin M
  • Hepatocyte Growth Factor
  • Trinitrobenzenesulfonic Acid