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PI3K Is a Linker Between L-selectin and PSGL-1 Signaling to IL-18 Transcriptional Activation at the Promoter Level

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Abstract

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.

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Acknowledgements

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.

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  1. School of Life Science, Shanxi University, 92 Wucheng Road, Taiyuan, China

    Jixian Luo

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Luo, J. PI3K Is a Linker Between L-selectin and PSGL-1 Signaling to IL-18 Transcriptional Activation at the Promoter Level. Inflammation 41, 555–561 (2018). https://doi.org/10.1007/s10753-017-0711-5

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