PMID- 12702049
OWN - NLM
STAT- MEDLINE
DCOM- 20031002
LR  - 20210712
IS  - 0815-9319 (Print)
IS  - 0815-9319 (Linking)
VI  - 18
IP  - 5
DP  - 2003 May
TI  - Enhanced intestinal inflammation induced by dextran sulfate sodium in tumor 
      necrosis factor-alpha deficient mice.
PG  - 560-9
AB  - BACKGROUND AND AIMS: Tumor necrosis factor-alpha (TNF-alpha) is a potent 
      pro-inflammatory cytokine thought to be involved in the pathogenesis of 
      inflammatory bowel disease. To further define the role of TNF-alpha in intestinal 
      inflammation, we studied the effects of dextran sulfate sodium (DSS) 
      administration in mice with targeted deletions of TNF-alpha gene. METHODS: Acute 
      colitis was induced in female TNF-alpha-/- and TNF-alpha+/+ mice by administering 
      4.5% DSS orally in drinking water for seven days. The colonic mucosal injury and 
      inflammation was evaluated based on body weight changes, total colon length, 
      luminal hemoglobin, and histological findings. Colonic mRNA expression for 
      inducible nitric oxide synthase (iNOS), TNF-alpha, interferon-gamma (IFN-gamma) 
      and interleukin-4 (IL-4) were measured by reverse transcription polymerase chain 
      reaction (RT-PCR), and nuclear factor kappaB (NF-kappaB) activation was evaluated 
      by electrophoretic mobility shift assay. RESULTS: In each assessment, colonic 
      injury was significantly aggravated in DSS-treated TNF-alpha-/- mice compared 
      with DSS-treated TNF-alpha+/+ mice. The survival rate of TNF-alpha-/- mice on day 
      seven was 40%; in contrast, all TNF-alpha+/+ mice were alive. Histological study 
      also showed an enhanced infiltration of inflammatory cells, especially 
      neutrophils, and mucosal cell disruption in DSS-treated TNF-alpha-/- mice 
      compared with DSS-treated TNF-alpha+/+ mice. On day seven, mRNA levels of 
      IFN-gamma and IL-4 in the colons of TNF-alpha-/- mice were faint or not detected; 
      in contrast, those of TNF-alpha+/+ mice were detected. Although the expression of 
      iNOS mRNA and luminal nitrite levels were similarly increased in both mice on day 
      seven, this induction was delayed in TNF-alpha-/- mice during the early phase. 
      The degree of NF-kappaB binding activity seemed to be similar between the two 
      types of mice on day seven. CONCLUSION: DSS-induced inflammation is significantly 
      enhanced in TNF-alpha-/- mice compared to TNF-alpha+/+ mice. These data suggest 
      that persistent and marked blockage of TNF-alpha bioactivity may provide a 
      detrimental effect on acute intestinal inflammation.
CI  - Copyright 2003 Blackwell Publishing Asia Pty Ltd
FAU - Naito, Yuji
AU  - Naito Y
AD  - First Department of Medicine, Kyoto Prefectural University of Medicine, 
      Kamigyo-Ku, Kyoto, Japan. ynaito@koto.kpu-m.ac.jp
FAU - Takagi, Tomohisa
AU  - Takagi T
FAU - Handa, Osamu
AU  - Handa O
FAU - Ishikawa, Takeshi
AU  - Ishikawa T
FAU - Nakagawa, Shuji
AU  - Nakagawa S
FAU - Yamaguchi, Taiji
AU  - Yamaguchi T
FAU - Yoshida, Norimasa
AU  - Yoshida N
FAU - Minami, Masato
AU  - Minami M
FAU - Kita, Masakazu
AU  - Kita M
FAU - Imanishi, Jiro
AU  - Imanishi J
FAU - Yoshikawa, Toshikazu
AU  - Yoshikawa T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Australia
TA  - J Gastroenterol Hepatol
JT  - Journal of gastroenterology and hepatology
JID - 8607909
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Colitis/*chemically induced/metabolism/pathology
MH  - Cytokines/genetics/metabolism
MH  - Dextran Sulfate/*toxicity
MH  - Female
MH  - Intestinal Mucosa/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase/genetics/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/deficiency/*physiology
EDAT- 2003/04/19 05:00
MHDA- 2003/10/03 05:00
CRDT- 2003/04/19 05:00
PHST- 2003/04/19 05:00 [pubmed]
PHST- 2003/10/03 05:00 [medline]
PHST- 2003/04/19 05:00 [entrez]
AID - 3034 [pii]
AID - 10.1046/j.1440-1746.2003.03034.x [doi]
PST - ppublish
SO  - J Gastroenterol Hepatol. 2003 May;18(5):560-9. doi: 
      10.1046/j.1440-1746.2003.03034.x.