Project 07

The role of sphingolipids in postoperative intestinal trauma

Study group van Echten-Deckert
Department of Surgery
Sigmund-Freud-Str. 25  l  53105 Bonn

Using a standardized surgical rodent model of intestinal manipulation we investigated the content of several sphingolipids (SLs) in the tunica muscularis externa as well as in the mucosa layer of rat bowel.

Interestingly, from all SLs analysed by LC-MS only an increase in the content of sphingosine-1-phosphate (S1P) and of ceramide-1-phosphate (C1P) in the intestinal tunica muscularis externa but not in the intestinal mucosa were observed. Both sphingolipid-phosphates belong to a class of bioactive lipids that play key roles in the regulation of several cellular processes including proliferation, differentiation, migration and adhesion. These cellular functions are essential for both, inflammatory and wound healing processes.

Indeed, our studies demonstrate that S1P and C1P enhance the production of prostaglandin E2 (PGE2) in primary cultured rat intestinal smooth muscle (RISM) cells by contributing to the modulation of the activity of COX2 and of PLA2, respectively. Moreover, S1P induced secretion of proinflammatory cytokines such as IL-1 and IL-6 in these cells.

We currently investigate whether mechanical stress, assumed to be causative for the local inflammatory processes in the intestinal muscularis, is correlated with increased levels of S1P and C1P. In addition, we try to further elucidate the molecular mechanisms underlying the proinflammatory action of S1P in RISM cells.

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