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Sphingosine-1-phosphate enhances IL-1{beta}-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts.
Am J Physiol Gastrointest Liver Physiol. 2008 Oct; 295(4):G766-75.AJ

Abstract

Intestinal subepithelial myofibroblasts (SEMFs) is a specific population of cells involved in intestinal inflammation and carcinogenesis via an elaborate network of cytokines, chemokines and other inflammatory factors, including PGE(2). Sphingosine-1-phosphate (S1P) has been implicated as an important mediator of inflammation and cancer and in certain cell types increases cyclooxygenase-2 (COX-2) expression. In the present study, we aimed to assess involvement of S1P in COX-2 expression by SEMFs. Primary SEMFs were obtained from C57BL/6J mouse and their identity was verified by fluorescent staining of specific marker proteins. Expression of S1P receptors 1, 2, 3 and sphingosine kinases 1 and 2 in SEMFs were determined by RT-PCR analysis. COX-2 expression and PGE(2) production were assayed by Western blotting and ELISA, respectively. COX-2 mRNA stability was assayed by Northern blotting. S1P produced dose-dependent increase in COX-2 expression, resulting in increased PGE(2) release from SEMFs. Using specific inhibitors, we show that actions of p38, ERK, IKK, and PKC were involved in S1P-induced COX-2 expression. On the other hand, p38 and PKC had lesser roles in IL-1beta-induced COX-2 expression. Inhibition of sphingosine kinase to block S1P production did not affect IL-1beta-induced COX-2 expression, but S1P amplified IL-1beta-induced p38 activation and COX-2 expression. PKC inhibition blocked S1P amplified COX-2 expression. S1P addition increased COX-2 mRNA stability. In SEMFs, S1P amplifies IL-1beta-induced COX-2 expression through increased mRNA stability. These observations point to involvement of S1P in activation of SEMFs that may contribute to intestinal inflammation and carcinogenesis.

Authors+Show Affiliations

Dept. of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The Univ. of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18703638

Citation

Ohama, Takashi, et al. "Sphingosine-1-phosphate Enhances IL-1{beta}-induced COX-2 Expression in Mouse Intestinal Subepithelial Myofibroblasts." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 295, no. 4, 2008, pp. G766-75.
Ohama T, Okada M, Murata T, et al. Sphingosine-1-phosphate enhances IL-1{beta}-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts. Am J Physiol Gastrointest Liver Physiol. 2008;295(4):G766-75.
Ohama, T., Okada, M., Murata, T., Brautigan, D. L., Hori, M., & Ozaki, H. (2008). Sphingosine-1-phosphate enhances IL-1{beta}-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts. American Journal of Physiology. Gastrointestinal and Liver Physiology, 295(4), G766-75. https://doi.org/10.1152/ajpgi.90423.2008
Ohama T, et al. Sphingosine-1-phosphate Enhances IL-1{beta}-induced COX-2 Expression in Mouse Intestinal Subepithelial Myofibroblasts. Am J Physiol Gastrointest Liver Physiol. 2008;295(4):G766-75. PubMed PMID: 18703638.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine-1-phosphate enhances IL-1{beta}-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts. AU - Ohama,Takashi, AU - Okada,Muneyoshi, AU - Murata,Takahisa, AU - Brautigan,David L, AU - Hori,Masatoshi, AU - Ozaki,Hiroshi, Y1 - 2008/08/14/ PY - 2008/8/16/pubmed PY - 2008/12/17/medline PY - 2008/8/16/entrez SP - G766 EP - 75 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 295 IS - 4 N2 - Intestinal subepithelial myofibroblasts (SEMFs) is a specific population of cells involved in intestinal inflammation and carcinogenesis via an elaborate network of cytokines, chemokines and other inflammatory factors, including PGE(2). Sphingosine-1-phosphate (S1P) has been implicated as an important mediator of inflammation and cancer and in certain cell types increases cyclooxygenase-2 (COX-2) expression. In the present study, we aimed to assess involvement of S1P in COX-2 expression by SEMFs. Primary SEMFs were obtained from C57BL/6J mouse and their identity was verified by fluorescent staining of specific marker proteins. Expression of S1P receptors 1, 2, 3 and sphingosine kinases 1 and 2 in SEMFs were determined by RT-PCR analysis. COX-2 expression and PGE(2) production were assayed by Western blotting and ELISA, respectively. COX-2 mRNA stability was assayed by Northern blotting. S1P produced dose-dependent increase in COX-2 expression, resulting in increased PGE(2) release from SEMFs. Using specific inhibitors, we show that actions of p38, ERK, IKK, and PKC were involved in S1P-induced COX-2 expression. On the other hand, p38 and PKC had lesser roles in IL-1beta-induced COX-2 expression. Inhibition of sphingosine kinase to block S1P production did not affect IL-1beta-induced COX-2 expression, but S1P amplified IL-1beta-induced p38 activation and COX-2 expression. PKC inhibition blocked S1P amplified COX-2 expression. S1P addition increased COX-2 mRNA stability. In SEMFs, S1P amplifies IL-1beta-induced COX-2 expression through increased mRNA stability. These observations point to involvement of S1P in activation of SEMFs that may contribute to intestinal inflammation and carcinogenesis. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/18703638/Sphingosine_1_phosphate_enhances_IL_1{beta}_induced_COX_2_expression_in_mouse_intestinal_subepithelial_myofibroblasts_ L2 - http://www.physiology.org/doi/full/10.1152/ajpgi.90423.2008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -