Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis

Tetsuji Kudo, Takayuki Matsumoto, Ikuo Nakamichi, Shinichiro Yada, Motohiro Esaki, Yukihiko Jo, Yutaka Ohji, Takashi Yao, Mitsuo Iida

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis). Material and methods. Murine colitis was induced by feeding with water containing 3% DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 μg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis. Results. Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01, <0.05, <0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001). Conclusions. Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.

Original languageEnglish
Pages (from-to)689-697
Number of pages9
JournalScandinavian Journal of Gastroenterology
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 30 2008

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Dextran Sulfate
Granulocyte Colony-Stimulating Factor
Colitis
Epithelial Cells
Apoptosis
Rectum
Phosphates
In Situ Nick-End Labeling
Inflammation
Descending Colon
Transverse Colon
Hematoxylin
Eosine Yellowish-(YS)
Crohn Disease
Weight Loss
Colon
Anti-Inflammatory Agents
Body Weight
Staining and Labeling
Water

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis. / Kudo, Tetsuji; Matsumoto, Takayuki; Nakamichi, Ikuo; Yada, Shinichiro; Esaki, Motohiro; Jo, Yukihiko; Ohji, Yutaka; Yao, Takashi; Iida, Mitsuo.

In: Scandinavian Journal of Gastroenterology, Vol. 43, No. 6, 30.06.2008, p. 689-697.

Research output: Contribution to journalArticle

Kudo, Tetsuji ; Matsumoto, Takayuki ; Nakamichi, Ikuo ; Yada, Shinichiro ; Esaki, Motohiro ; Jo, Yukihiko ; Ohji, Yutaka ; Yao, Takashi ; Iida, Mitsuo. / Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis. In: Scandinavian Journal of Gastroenterology. 2008 ; Vol. 43, No. 6. pp. 689-697.
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abstract = "Objective. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis). Material and methods. Murine colitis was induced by feeding with water containing 3{\%} DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 μg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis. Results. Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01, <0.05, <0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001). Conclusions. Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.",
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T1 - Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis

AU - Kudo, Tetsuji

AU - Matsumoto, Takayuki

AU - Nakamichi, Ikuo

AU - Yada, Shinichiro

AU - Esaki, Motohiro

AU - Jo, Yukihiko

AU - Ohji, Yutaka

AU - Yao, Takashi

AU - Iida, Mitsuo

PY - 2008/6/30

Y1 - 2008/6/30

N2 - Objective. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis). Material and methods. Murine colitis was induced by feeding with water containing 3% DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 μg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis. Results. Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01, <0.05, <0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001). Conclusions. Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.

AB - Objective. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis). Material and methods. Murine colitis was induced by feeding with water containing 3% DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 μg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis. Results. Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01, <0.05, <0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001). Conclusions. Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.

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