Effects of sphingosine-1-phosphate and ceramide-1-phosphate on rat intestinal smooth muscle cells: implications for postoperative ileus.

Abstract

Postoperative ileus, a major cause of morbidity after abdominal surgery, is characterized by intestinal dysmotility and inflammation. The aim was to investigate the involvement of sphingolipids in postoperative intestinal inflammation using a standardized rat model of intestinal surgical manipulation. Sphingolipid analysis (ESI-MS) of intestinal muscularis after manipulation revealed a time-dependent increase of sphingosine 1-phosphate (S1P) and of ceramide 1-phosphate (C1P). We therefore established a culture system of primary rat intestinal smooth muscle cells and examined the potential role of these sphingolipids in intestinal inflammation. Incubation of cells with either of the two sphingolipid-phosphates resulted in an elevated production of PGE(2). Further analysis revealed that S1P enhances cyclooxygenase 2 (COX-2) expression whereas C1P increases release of arachidonic acid, indicating an enhanced phospholipase A(2) activity. S1P-induced COX-2 expression was pertussis toxin sensitive, suggesting the involvement of Gi/o protein-coupled S1P receptors. Further downstream mediators of S1P induced COX-2 expression appear to be extracellular regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). Collectively, our results demonstrate that intestinal smooth muscle cells represent a major target for both C1P and S1P activity. Thus, the sustained elevated concentration of the two bioactive sphingolipids in this tissue could at least in part explain postoperative intestinal dysmotility.

• Authors: Mihaela Dragusin, Sven Wehner, Samuel Kelly, Elaine Wang, Alfred H Merrill Jr, Jörg C Kalff, Gerhild van Echten-Deckert
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 20 Issue 11 Pg. 1930-2 (Sep 2006) ISSN: 1530-6860 [Electronic] United States
• PMID: 16877527 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ceramides
• Lysophospholipids
• ceramide 1-phosphate
• sphingosine 1-phosphate
• Arachidonic Acid
• Cyclooxygenase 2
• Phospholipases A
• Sphingosine

Topics

• Animals
• Arachidonic Acid (metabolism)
• Cells, Cultured
• Ceramides (pharmacology)
• Cyclooxygenase 2 (metabolism)
• Enzyme Activation
• Ileus (etiology, physiopathology)
• Intestines (drug effects, physiology, surgery)
• Lysophospholipids (pharmacology)
• Muscle, Smooth (drug effects, physiology, surgery)
• Phospholipases A (metabolism)
• Postoperative Complications
• Rats
• Sphingosine (analogs & derivatives, pharmacology)