PI3K Is a Linker Between L-selectin and PSGL-1 Signaling to IL-18 Transcriptional Activation at the Promoter Level
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.
KEY WORDSinflammation adhesion molecules signal transduction pro-inflammatory cytokines
This work was supported by the National Natural Science Foundation of China (31401216) and Research Project Supported by Shanxi Scholarship Council of China (2017-012). We appreciate Shanzhi Wang for all his work in the manuscript revision, including reading, editing, and revising in detail.
Compliance with Ethical Standards
Conflict of interest
The author declares that he has no conflict of interest.
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