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 (LPA(3)) are coordinately up-regulated in LPS-stimulated THP-1 cells. PKR-mediated activation of JNK1 and p38 MAPK is required for both ATX and LPA(3) 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 LPA(3) up-regulation. Either ATX or LPA(3) knockdown inhibited CCL8 induction by LPS, suggesting that ATX and LPA(3) are involved in CCL8 induction during the inflammatory process against bacterial infection.
The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
Song
S
Li
Chaoyang
C
Xiong
Junjie
J
Zhang
D002460:Cell Line; D054412:Chemokine CCL8 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008246:Lysophospholipids / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099157:Sphingosine Kinase; D000099189:Lysophospholipase D
D054412:Chemokine CCL8; D048049:Extracellular Signal-Regulated MAP Kinases; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D048055:Mitogen-Activated Protein Kinase 8; D019869:Phosphatidylinositol 3-Kinases; D010727:Phosphoric Diester Hydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid; D051176:beta Catenin; D019892:eIF-2 Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D000099157:Sphingosine Kinase; D000099189:Lysophospholipase D; C515453:CCL8 protein, human; C032881:lysophosphatidic acid