L-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are adhesion molecules which induce similar physiological events. Our previous paper showed that phosphatidylinositol 3-kinase (PI3K) played a crucial role in L-selectin- and PSGL-1-mediated F-actin redistribution and assembly during neutrophil rolling on E-selectin. However, it is not clear whether L-selectin and PSGL-1 induce other similar physiology events by PI3K. Here, we investigated the possibility of PI3K linking the signaling pathways of L-selectin and PSGL-1 to IL-18 transcription. We first demonstrated that L-selectin and PSGL-1 stimulation upregulated IL-18 transcription level in Jurkat cells. Then we found that PI3K inhibitor LY294002 reduced L-selectin- and PSGL-1-induced mRNA upregulation of IL-18 in Jurkat cells. Transfection of phosphatase and tensin homolog expressing plasmid inhibited the transcription level of IL-18. Therefore, PI3K is a signal linker between L-selectin and PSGL-1 in IL-18 transcriptional activation at the promoter level. To our knowledge, this is the first time to directly link PI3K to L-selectin- and PSGL-1-mediated IL-18 transcription, providing a foundation for intervention of PI3K-related inflammation.
Keywords: adhesion molecules; inflammation; pro-inflammatory cytokines; signal transduction.