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Inflammopharmacology. 2010 Apr;18(2):73-85. doi: 10.1007/s10787-010-0032-x. Epub 2010 Feb 12.

Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn's disease.

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  • 1Apogee Biotechnology Corporation, Hershey Center for Applied Research, 1214 Research Blvd, Suite 1016, Hummelstown, PA 17036, USA. LWMaines@apogee-biotech.com

Abstract

AIM:

Activation of sphingosine kinase (SK) is a key response to many inflammatory processes. The present studies test the hypothesis that an orally available SK inhibitor, ABC294640, would be effective in rodent models of Crohn's disease.

METHODS:

Trinitrobenzene sulfonic acid (TNBS) was administered rectally to mice and rats. Rats were treated with ABC294640 orally alone or in combination with olsalazine and disease progression was monitored.

RESULTS:

For both rodent species, treatment with ABC294640 attenuated disease progression. Colon samples from the ABC294640-treated animals had improved histology and cytokine parameters when compared with vehicle-treated animals. The expression of SK was similarly increased in TNBS-treated animals and in human colon tissue specimens from inflammatory bowel disease patients relative to normal, control patients.

CONCLUSIONS:

Sphingosine kinase may be a critical mediator of colonic damage during intestinal inflammation, and pharmacologic inhibitors of this enzyme may prove useful in the treatment of Crohn's disease.

PMID:
20151210
[PubMed - indexed for MEDLINE]

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