| Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn's disease. | |
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MedLine Citation:
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PMID: 20151210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Lynn W Maines; Leo R Fitzpatrick; Cecelia L Green; Yan Zhuang; Charles D Smith |
Publication Detail:
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Type: Journal Article Date: 2010-02-12 |
Journal Detail:
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Title: Inflammopharmacology Volume: 18 ISSN: 1568-5608 ISO Abbreviation: Inflammopharmacology Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-15 Completed Date: 2010-09-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9112626 Medline TA: Inflammopharmacology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 73-85 Citation Subset: IM |
Affiliation:
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Apogee Biotechnology Corporation, Hershey Center for Applied Research, 1214 Research Blvd, Suite 1016, Hummelstown, PA 17036, USA. LWMaines@apogee-biotech.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adamantane
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administration & dosage,
analogs & derivatives,
pharmacology,
therapeutic use Aminosalicylic Acids / administration & dosage, pharmacology, therapeutic use Animals Body Weight / drug effects Colon / drug effects, enzymology, metabolism, pathology Crohn Disease / chemically induced*, drug therapy*, metabolism, pathology Disease Models, Animal Drug Therapy, Combination Enzyme Inhibitors / pharmacology, therapeutic use* Epithelial Cells / enzymology, metabolism Female Gastrointestinal Agents / administration & dosage, pharmacology, therapeutic use Humans Interleukin-1beta / metabolism Leukocytes / enzymology, metabolism Male Mice Mice, Inbred C57BL Neutrophils / enzymology, pathology Peroxidase / metabolism Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*, metabolism Prednisolone / administration & dosage, pharmacology, therapeutic use Pyridines / administration & dosage, pharmacology, therapeutic use Rats Rats, Sprague-Dawley Treatment Outcome Trinitrobenzenesulfonic Acid / administration & dosage, pharmacology Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide; 0/Aminosalicylic Acids; 0/Enzyme Inhibitors; 0/Gastrointestinal Agents; 0/Interleukin-1beta; 0/Pyridines; 0/Tumor Necrosis Factor-alpha; 15722-48-2/olsalazine; 2508-19-2/Trinitrobenzenesulfonic Acid; 281-23-2/Adamantane; 50-24-8/Prednisolone; EC 1.11.1.7/Peroxidase; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/sphingosine kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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