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Sphingosine 1-phosphate induces inflammation and osteogenesis and increases the activity of the LPS/TLR4 route in human aortic valve interstitial cells

AuthorsFernández-Pisonero, I.; López, Javier ; Dueñas, Ana I. ; Maeso, Patricia; Varona, Saray; Gómez, Cristina ; García-Rodríguez, Carmen
Issue Date2012
Citation22nd IUBMB - 37th FEBS Congress (2012)
Abstract[Aims]: Lipid accumulation in the aortic valve is a characteristic of aortic stenosis and sphingosine 1-phosphate (S1P) plays a relevant functional role in the cardiovascular system. On this basis, we investigated the possible role of S1P on the induction of proinflammatory and pro-osteogenic changes in human interstitial cells from aortic valve (AVIC) and pulmonary valves (PVIC). [Methods and Results]: As regards pro-inflammatory routes, S1P up-regulated IL-6, IL-8, and cyclooxygenase (COX)-2 in AVICs, as determined by Western blot and ELISA experiments. AVIC exposure to a combination of S1P and bacterial lipopolysaccharide (LPS) a Toll-like receptor (TLR)-4 ligand known to promote pro-inflammatory and pro-osteogenic phenotypes in AVICs, resulted in the synergistic induction of COX-2, PGE2, and intercellular adhesion molecule (ICAM)-1. Strikingly, the cooperative effect was stronger in stenotic than in control cells, and more prominent in cells from the aortic valves than from the pulmonary valves, which rarely undergo stenosis. Pharmacological and gene silencing experiments revealed the involvement of several S1P receptors in the synergistic effect. As regards proosteogenic processes, S1P induced the expression/activity of the calcification marker alkaline phosphatase (ALP) in in vitro calcification experiments. In addition, S1P cooperated with LPS to enhance significantly ALP activity and the cooperative effect was partially blocked by S1P receptor antagonists. [Conclusions]: S1P induces pro-inflammatory and pro-osteogenic changes and increases the effect of TLR4 ligands in AVICs, what might be relevant for the pathogenesis of aortic stenosis and could open the way for new therapeutic approaches for this disease.
DescriptionResumen del póster presentado al 22nd IUBMB & 37th FEBS Congress: "From Single Molecules to Systems Biology" celebrado en Sevilla (España) del 4 al 9 de septiembre de 2012.-- et al.
Appears in Collections:(IBGM) Comunicaciones congresos
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