A role for sphingosine kinase 1 in dextran sulfate sodium‐induced colitis
| Autor: | Ashley J. Snider, Toshihiko Kawamori, Gary S. Gilkeson, Yusuf A. Hannun, Sarah G. Bradshaw, K. Alexa Orr, Lina M. Obeid |
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| Rok vydání: | 2008 |
| Předmět: |
Erythrocytes
Colon Sphingosine kinase Inflammation Pharmacology Biology Biochemistry Inflammatory bowel disease Research Communications Mice chemistry.chemical_compound Sphingosine Genetics medicine Animals Humans Sphingosine-1-phosphate Colitis Molecular Biology Mice Knockout Tumor Necrosis Factor-alpha Body Weight Dextran Sulfate Organ Size medicine.disease Mice Inbred C57BL Phosphotransferases (Alcohol Group Acceptor) Gene Expression Regulation chemistry Sphingosine kinase 1 Cyclooxygenase 2 Immunology biology.protein Colitis Ulcerative Tumor necrosis factor alpha Lysophospholipids medicine.symptom Spleen Biotechnology |
| Zdroj: | The FASEB Journal. 23:143-152 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.08-118109 |
| Popis: | The bioactive lipid sphingosine-1-phosphate (S1P) is emerging as an important mediator of immune and inflammatory responses. S1P formation is catalyzed by sphingosine kinase (SK), of which the SK1 isoenzyme is activated by tumor necrosis alpha (TNF-α). SK1 has been shown to be required for mediating TNF-α inflammatory responses in cells, including induction of cyclooxygenase 2 (COX-2). Because TNF-α and COX-2 are increased in patients with inflammatory bowel disease (IBD), we investigated the role of SK1 in a murine model of colitis. SK1−/− mice treated with dextran sulfate sodium (DSS) had significantly less blood loss, weight loss, colon shortening, colon histological damage, and splenomegaly than did wild-type (WT) mice. In addition, SK1−/− mice had no systemic inflammatory response. Moreover, WT but not SK1−/− mice treated with dextran sulfate sodium had significant increases in blood S1P levels, colon SK1 message and activity, and colon neutrophilic infiltrate. Unlike WT mice, SK1−/− mice failed to show colonic COX-2 induction despite an exaggerated TNF-α response; thus implicating for the first time SK1 in TNF-α-mediated COX-2 induction in vivo. Inhibition of SK1 may prove to be a valuable therapeutic target by inhibiting systemic and local inflammation in IBD.—Snider, A. J., Kawamori, T., Bradshaw, S. G., Orr, K. A., Gilkeson, G. S., Hannun, Y. A., Obeid, L. M. A role for sphingosine kinase 1 in dextran sulfate sodium-induced colitis. |
| Databáze: | OpenAIRE |
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