PMID- 12164961
OWN - NLM
STAT- MEDLINE
DCOM- 20021119
LR  - 20190901
IS  - 0815-9319 (Print)
IS  - 0815-9319 (Linking)
VI  - 17
IP  - 8
DP  - 2002 Aug
TI  - Inhibitory effects of the new anti-inflammatory agent, IS-741, on spontaneous 
      colitis in HLA-B27/beta2-microglobulin transgenic rats.
PG  - 854-60
AB  - BACKGROUND: A novel anti-inflammatory drug, IS-741, blocked the adhesion of 
      inflammatory cells to microvascular endothelial cells both in vivo and in vitro. 
      Transgenic rats expressing human leukocyte antigen (HLA)-B27 and human 
      beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis, which 
      resembles human inflammatory bowel disease. In the present study, the authors 
      examined the efficacy of IS-741 against spontaneous colitis in HLA-B27 rats. 
      METHODS: The HLA-B 27 rats were divided in two groups after the development of 
      colitis. IS-741 was dissolved in water and administered orally (10 mg/kg) once 
      per day for 14 days. RESULTS: The HLA-B27 rats treated with IS-741 remained 
      healthy; the wet weight of the colon was significantly lower in the 
      IS-741-treated group. Histological examinations revealed a marked infiltration of 
      inflammatory cells into both the mucosa and the submucosa in the control HLA-B27 
      rats, but these changes were attenuated in the IS-741-treated group. The mucosal 
      damage score was also significantly reduced by treatment with IS-741. IS-741 
      significantly reduced the mucosal myeloperoxidase activity and mucosal 
      cytokine-induced neutrophil chemoattractant-1 levels. IS-741 also reduced 
      CD3-positive T-cell infiltration. CONCLUSION: IS-741 suppressed the spontaneous 
      colitis that developed in HLA-B27 rats. Some of the actions of IS-741 may be 
      associated with its inhibitory effects on the adhesion of neutrophils to 
      endothelial cells. The findings from the present study suggest that IS-741 may be 
      a useful new therapeutic agent for inflammatory bowel disease.
FAU - Makino, Jin
AU  - Makino J
AD  - Division of Gastroenterology, Shiga University of Medical Science, Otsu, Japan.
FAU - Andoh, Akira
AU  - Andoh A
FAU - Hata, Kazunori
AU  - Hata K
FAU - Yotsuya, Shuichi
AU  - Yotsuya S
FAU - Shikama, Hiroshi
AU  - Shikama H
FAU - Imamura, Masashi
AU  - Imamura M
FAU - Fujiyama, Yoshihide
AU  - Fujiyama Y
FAU - Bamba, Tadao
AU  - Bamba T
LA  - eng
PT  - Journal Article
PL  - Australia
TA  - J Gastroenterol Hepatol
JT  - Journal of gastroenterology and hepatology
JID - 8607909
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Pyridines)
RN  - 0 (beta 2-Microglobulin)
RN  - 03TE67E8IR (IS 741)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified/*genetics
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Colitis/*drug therapy/*genetics/pathology
MH  - Disease Models, Animal
MH  - HLA-B27 Antigen/*genetics
MH  - Lymphocyte Count
MH  - Male
MH  - Pyridines/*therapeutic use
MH  - Rats/genetics
MH  - beta 2-Microglobulin/*genetics
EDAT- 2002/08/08 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/08/08 10:00
PHST- 2002/08/08 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/08/08 10:00 [entrez]
AID - 2815 [pii]
AID - 10.1046/j.1440-1746.2002.02815.x [doi]
PST - ppublish
SO  - J Gastroenterol Hepatol. 2002 Aug;17(8):854-60. doi: 
      10.1046/j.1440-1746.2002.02815.x.