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 Requena, Javier
A1 Balboa García, María Ángeles
A1 Balsinde Rodríguez, 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 14-mar-2025