ATX and LPA receptor 3 are coordinately up-regulated in lipopolysaccharide-stimulated THP-1 cells through PKR and SPK1-mediated pathways

Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation and immunity. Previously, we showed that autotaxin (ATX), the enzyme producing LPA from lysophosphatidylcholine (LPC), is induced by LPS in THP-1 cells via the activation of PKR, JNK and p38 MAPK. In this study, we find that ATX and LPA receptor 3 (LPA3) are coordinately up-regulated in LPS-stimulated THP-1 cells. PKR-mediated activation of JNK1 and p38 MAPK is required for both ATX and LPA3 up-regulation. SPK1-mediated activation of the PI3K-AKT-β-catenin pathway is essential for ATX induction, while SPK1-mediated ERK activation is required for LPA3 up-regulation. Either ATX or LPA3 knockdown inhibited CCL8 induction by LPS, suggesting that ATX and LPA3 are involved in CCL8 induction during the inflammatory process against bacterial infection.

► ATX and LPA3 are coordinately up-regulated by LPS in human monocytic THP-1 cells.
► PKR-mediated JNK1 and p38 MAPK activation is required for ATX and LPA3 induction.
► SPK1-mediated PI3K–AKT–β-catenin pathway activation is required for ATX induction.
► SPK1-mediated ERK activation is required for LPA3 up-regulation by LPS in THP-1 cells.
► Either ATX or LPA3 knockdown inhibits the CCL8 induction by LPS in THP-1 cells.