Ameliorating effect of hepatocyte growth factor on inflammatory bowel disease in a murine model.
Hepatocyte growth factor (HGF), a multifunctional cytokine, accelerates intestinal epithelial proliferation. We studied the effects of HGF in mice with trinitrobenzene sulfonic acid-induced colitis, which shows clinical and molecular resemblance to Crohn's disease. Mice with colitis repeatedly were transfected intramuscularly with human HGF cDNA. Weight, survival, histopathology, proinflammatory cytokine mRNAs, and leukocyte infiltration were assessed. Treatment with HGF cDNA induced tyrosine phosphorylation of intestinal c-Met/HGF receptors, inhibited apoptosis, and promoted mitosis in intestinal epithelial cells, accelerating intestinal epithelial restoration and suppressing inflammation. Transfection with HGF cDNA markedly suppressed intestinal mRNA expression of T-helper 1 cytokines such as interleukin-12 and -1beta, interferon-gamma, and tumor necrosis factor-alpha. Numbers of total and CD4-positive T cells, neutrophils, and myloperoxidase activity in intestinal epithelium were diminished by HGF gene transfer, which also prevented weight loss, and improved survival. HGF might prove useful for controlling inflammatory bowel disease.
Oh
Koushi
K
First Dept. of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Iimuro
Yuji
Y
Takeuchi
Masaharu
M
Kaneda
Yasufumi
Y
Iwasaki
Tsuyoshi
T
Terada
Nobuyuki
N
Matsumoto
Takayuki
T
Nakanishi
Kenji
K
Fujimoto
Jiro
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D014162:Transfection; D014302:Trinitrobenzenesulfonic Acid; D015431:Weight Loss / Q000187:drug effects
D016207:Cytokines; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase