RT info:eu-repo/semantics/article
T1 Group V Phospholipase A2-Derived Lysophosphatidylcholine Mediates Cyclooxygenase-2 Induction in Lipopolysaccharide-Stimulated Macrophages
A1 Ruipérez Prádanos, Violeta
A1 Casas, Javier
A1 Balboa, María A.
A1 Balsinde, Jesús
AB Activation of macrophages and macrophage cell lines by bacterial LPS elicits a delayed phase of PG biosynthesis that appears to be entirely mediated by cyclooxygenase-2 (COX-2). In previous work, we found that a catalytically active group V secreted phospholipase A2 (sPLA2-V) was required for COX-2 induction, but the nature of the sPLA2-V metabolite involved was not defined. In this study, we identify lysophosphatidylcholine (lysoPC) as the sPLA2-V downstream mediator involved in COX-2 induction by LPS-stimulated macrophages. Inhibition of sPLA2-V by RNA interference or by the cell-permeable compound scalaradial blocked LPS-induced COX-2 expression, and this inhibition was overcome by incubating the cells with a nonhydro- lyzable lysoPC analog, but not by arachidonic acid or oleic acid. Moreover, inhibition of sPLA2-V by scalaradial also prevented the activation of the transcription factor c-Rel, and such an inhibition was also selectively overcome by the lysoPC analog. Collectively, these results support a model whereby sPLA2-V hydrolysis of phospholipids upon LPS stimulation results in lysoPC generation, which in turn regulates COX-2 expression by a mechanism involving the transcriptional activity of c-Rel.
SN 0022-1767
YR 2007
FD 2007
LK https://uvadoc.uva.es/handle/10324/64292
UL https://uvadoc.uva.es/handle/10324/64292
LA eng
NO Journal of immunology (Baltimore, Md : 1950) 179, 631–638 (2007).
NO Producción Científica
DS UVaDOC
RD 19-may-2024