Apoptotic Cell-Derived Sphingosine-1-Phosphate Promotes HuR-Dependent Cyclooxygenase-2 mRNA Stabilization and Protein Expression

Johann, Axel M.; Weigert, Andreas; Eberhardt, W.; Kühn, Alfred; Barra, Vera; Knethen, Andreas von; Pfeilschifter, Josef; Brüne, Bernhard

doi:10.4049/jimmunol.180.2.1239

Cited by 49 publications

(34 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although S1P is known to directly pass through a plasma membrane and may act as an intracellular second messenger with direct targets that are as yet unknown (2,39), our finding that upregulation of COX-2 by S1P was completely blocked by PTX that inactivates Gi protein indicates that S1P-induced COX-2 expression is mediated through S1P receptors in mouse SEMFs. Although we observed PGE 2 release from SEMFs by S1P treatment, the very recent report using RAW264.7 mouse macrophage-like cell line demonstrates that S1P induced COX-2 expression but not PGE 2 production, because of the lack of phospholipase A2 activation (18).…”

Section: Discussioncontrasting

confidence: 87%

“…It is recently reported that HETES enhance IL-1-mediated COX-2 expression via p38 and HuR-dependent augmentation of mRNA stability in 18Co human SEMF cell line (11). Moreover, S1P promotes HuR-dependent COX-2 mRNA stabilization in RAW264.7 mouse macrophage-like cell line (18). Therefore we expect that, in mouse SEMFs, S1P induced activation of p38 and PKC leads to COX-2 mRNA stabilization by HuR-dependent mechanism.…”

Section: Discussionmentioning

confidence: 83%

See 1 more Smart Citation

Sphingosine-1-phosphate enhances IL-1β-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts

Okada¹,

Murata²,

Brautigan³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Ohama T, Okada M, Murata T, Brautigan DL, Hori M, Ozaki H. Sphingosine-1-phosphate enhances IL-1␤-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts. Am J Physiol Gastrointest Liver Physiol 295: G766 -G775, 2008. First published August 14, 2008 doi:10.1152/ajpgi.90423.2008 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-1␤-induced COX-2 expression. Inhibition of sphingosine kinase to block S1P production did not affect IL-1␤-induced COX-2 expression, but S1P amplified IL-1␤-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-1␤-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. cyclooxygenase 2; sphingosine kinase; curcumin; Protein kinase C; mRNA stability UNDER THE EPITHELIUM OF THE gastrointestinal tract, intestinal subepithelial myofibroblasts (SEMFs) form a cellular network from the esophagus to the anus. These SEMFs exhibit the ultrastructural features of both fibroblasts and smooth muscle cells and are characterized by positive immunoreactivity for ␣-smooth muscle actin (␣-SMA) and vimentin (3, 37). SEMFs are distinguished from smooth muscle cells, which express ␣-SMA but are negative for vimentin. SEMFs are classified as members of a family of functionally related cells, including hepatic stellate cells (Ito cells), glomerular mesangial cells, and orbital and synovial fibroblasts (41).It is thought that various factors produced by SEMFs, including growth factors, proinflammatory cytokines, matrix protein, and prostaglandins (PGs), play an important role in mucosal repair, inflammatory response, and carcinogenesis of the intestine (3, 37). PGs are derived from arachidonic acid (AA), which is a polyunsaturated fatty acid (C20:4) released from cell membrane pho...

show abstract

Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 83%

Sphingosine-1-phosphate enhances IL-1β-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts

Okada¹,

Murata²,

Brautigan³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…We have shown previously that cyclooxygenase-2 is up-regulated under hypoxia in a HIF-1-independent fashion (5). It is interesting to note that S1P is a potent inducer of cyclooxygenase-2 expression (22,47), thus opening the possibility that S1P is responsible for cyclooxygenase-2 induction and the formation of antiapoptotic prostaglandin E 2 under hypoxia. This might help to understand how signaling pathways cooperate in cell protection within hypoxic tumor regions.…”

Section: Cm(hypoxia)mentioning

confidence: 99%

Hypoxia Enhances Sphingosine Kinase 2 Activity and Provokes Sphingosine-1-Phosphate-Mediated Chemoresistance in A549 Lung Cancer Cells

Schnitzer

Weigert

Zhou

et al. 2009

Molecular Cancer Research

Self Cite

View full text Add to dashboard Cite

Hypoxia and signaling via hypoxia-inducible factor-1 (HIF-1) is a key feature of solid tumors and is related to tumor progression as well as treatment failure. Although it is generally accepted that HIF-1 provokes tumor cell survival and induces chemoresistance under hypoxia, HIF-1-independent mechanisms operate as well. We present evidence that conditioned medium obtained from A549 cells, incubated for 24 h under hypoxia, protected naive A549 cells from etoposide-induced cell death. Lipid extracts generated from hypoxiaconditioned medium still rescued cells from apoptosis induced by etoposide. Specifically, the bioactive lipid sphingosine-1-phosphate (S1P) not only was essential for cell viability of A549 cells but also protected cells from apoptosis. We noticed an increase in sphingosine kinase 2 (SphK2) protein level and enzymatic activity under hypoxia, which correlated with the release of S1P into the medium. Knockdown of SphK2 using specific small interfering RNA relieved chemoresistance of A549 cells under hypoxia and conditioned medium obtained from SphK2 knockdown cells was only partially protective. Coincubations of conditioned medium with VPC23019, a S1P 1 /S1P 3 antagonist, reduced protection of conditioned medium, with the further notion that p42/ 44 mitogen-activated protein kinase transmits autocrine or paracrine survival signaling downstream of S1P 1 /S1P 3 receptors. Our data suggest that hypoxia activates SphK2 to promote the synthesis and release of S1P, which in turn binds to S1P 1 /S1P 3 receptors, thus activating p42/44 mitogen-activated protein kinase to convey autocrine or paracrine protection of A549 cells.

show abstract

“…It is thought that COX-2 inhibitors prevent the development of resistance to different cytostatics and that COX-2 overexpression induces increased multidrug resistance protein 1 (MRP1) expression in different cancer cells [99][100][101][102] . Schnitzer et al showed that COX-2 is upregulated under hypoxia in a HIF-1-independent fashion and sphingosine-1-phosphate (S1P) is responsible for COX-2 induction under hypoxia in A549 lung cancer cells 103 . Simultaneous inhibition of HIF-1 and COX-2 strongly suppresses chemoresistance and the inhibition of only COX-2 decreases chemoresistance of cancer cells in hypoxia 33 .…”

mentioning

confidence: 99%

Hypoxia-induced chemoresistance in cancer cells: The role of not only HIF-1

Doktorova

Hraběta

Khalil

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Background. The aim of this review is to provide the information about molecular basis of hypoxia-induced chemoresistance, focusing on the possibility of diagnostic and therapeutic use. Results. Hypoxia is a common feature of tumors and represents an independent prognostic factor in many cancers. It is the result of imbalances in the intake and consumption of oxygen caused by abnormal vessels in the tumor and the rapid proliferation of cancer cells. Hypoxia-induced resistance to cisplatin, doxorubicin, etoposide, melphalan, 5-flouoruracil, gemcitabine, and docetaxel has been reported in a number of experiments. Adaptation of tumor cells to hypoxia has important biological effects. The most studied factor responsible for these effects is hypoxia-inducible factor-1 (HIF-1) that significantly contributes to the aggressiveness and chemoresistance of different tumors. The HIF-1 complex, induced by hypoxia, binds to target genes, thereby increasing the expression of many genes. In addition, the expression of hundreds of genes can be also decreased in response to hypoxia in HIF-1 dependent manner, but without the detection of HIF-1 in these genes' promoters. HIF-1 independent mechanisms for drug resistance in hypoxia have been described, however, they are still rarely reported. The first clinical studies focusing on diagnosis of hypoxia and on inhibition of hypoxia-induced changes in cancer cells are starting to yield results. Conclusions. The adaptation to hypoxia requires many genetic and biochemical responses that regulate one another. Hypoxia-induced resistance is a very complex field and we still know very little about it. Different approaches to circumvent hypoxia in tumors are under development.

show abstract

Apoptotic Cell-Derived Sphingosine-1-Phosphate Promotes HuR-Dependent Cyclooxygenase-2 mRNA Stabilization and Protein Expression

Cited by 49 publications

References 47 publications

Sphingosine-1-phosphate enhances IL-1β-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts

Sphingosine-1-phosphate enhances IL-1β-induced COX-2 expression in mouse intestinal subepithelial myofibroblasts

Hypoxia Enhances Sphingosine Kinase 2 Activity and Provokes Sphingosine-1-Phosphate-Mediated Chemoresistance in A549 Lung Cancer Cells

Hypoxia-induced chemoresistance in cancer cells: The role of not only HIF-1

Contact Info

Product

Resources

About