Signaling in lipopolysaccharide-induced stabilization of formyl peptide receptor 1 mRNA in mouse peritoneal macrophages.

摘要: To identify the TLR4-initiated signaling events that couple to formyl peptide receptor (FPR)1 mRNA stabilization, macrophages were treated with LPS along a selection of compounds targeting several known pathways. Although inhibitors protein tyrosine kinases, MAPKs, and stress-activated kinases had little or no effect on response LPS, LY294002 (LY2) parthenolide (an IκB kinase inhibitor) both potent inhibitors. LY2 but not blocked LPS-induced stabilization FPR1 mRNA. wortmannin effectively PI3K activity, expression did modulate decay Moreover, although was demonstrated be inhibitor structural analog LY2, LY303511 (LY3), which inhibit PI3K, equally effective at preventing LPS-stimulated expression. The mammalian target rapamycin activity (measured as phospho-p70S6 kinase) activated by significantly LY2. In addition, mTOR it Finally, mechanisms involved in could distinguished from those AU-rich mRNAs because prolonged half-life insensitive inhibition p38 MAPK. These findings demonstrate LY2/LY3 targets novel TLR4-linked pathway selectively couples