Article thumbnail

Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis

By Yasuaki Sanada, Tsunekazu Mizushima, Yasuyuki Kai, Junichi Nishimura, Hiroshi Hagiya, Haruto Kurata, Hirotaka Mizuno, Etsuko Uejima and Toshinori Ito


Although IL-17 is a pro-inflammatory cytokine reportedly involved in various autoimmune inflammatory disorders, its role remains unclear in murine models of colitis. Acute colitis was induced by 2.5% dextran sodium sulfate (DSS) treatment for 5 days. A novel sphingosine-1-phosphate receptor agonist W-061, a prototype of ONO-4641, was orally administered daily, and histopathological analysis was performed on the colon. The number of lymphocytes and their cytokine production were also evaluated in spleen, mesenteric lymph node, Peyer's patch and lamina propria of the colon. Daily administration of W-061 resulted in improvement of DSS-induced colitis, and significantly reduced the number of CD4+ T cells in the colonic lamina propria. Numbers of both Th17 and Th1 cells were reduced by W-061 treatment. W-061, however, had no influence on the number of Treg cells in lamina propria. Thus, Th17 and Th1 cells in lamina propria were thought to be the key subsets in the pathogenesis of DSS-induced colitis. In conclusion, W-061 may be a novel therapeutic strategy to ameliorate acute aggravation of inflammatory bowel diseases

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2006). AntiTNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials.
  2. (2009). Autoimmune T cell responses in the central nervous system.
  3. (2007). Carding SR. Inflammatory bowel disease: cause and immunobiology.
  4. (1996). Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5.
  5. (2009). Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBSinduced colitis.
  6. (2009). IL-17 as a future therapeutic target for rheumatoid arthritis.
  7. (2003). Increased expression of interleukin 17 in inflammatory bowel disease.
  8. (2010). Infliximab, azathioprine, or combination therapy for Crohn’s disease.
  9. (2008). Involvement of IL17A in the pathogenesis of DSS-induced colitis in mice.
  10. (1999). of cytokine expression in the rectal mucosa of ulcerative colitis: correlation with disease activity.
  11. (2008). Th17 cell differentiation: the long and winding road.
  12. (2008). Th17 cells in human disease.