Inhibitory Effects of Lysophospholipids on Survival and Interleukin-8 Secretion of HT-29, a Human Colon Cancer-Derived Epithelial Cell

Lysophpsphospholipids (LPLs) are lipid mediators involved in various physiological functions. In daily diets, people consume large amounts of various lipids, including LPLs. Exogenous dietary LPLs initially affect epithelial cells and, finally, the entire colon and may be linked to the onset and prevention of colonic diseases, including inflammatory bowel disease. However, the effects of exogenous LPLs on epithelial cells remain poorly understood. In this study, we used HT-29, a human colon cancer-derived epithelial cell, to evaluate the effects of LPLs on epithelial cells under normal and inflammatory states. In the absence of lipopolysaccharide (LPS), several LPLs decreased interleukin-8 (IL-8) secretion from HT-29 cells in the following order of potency based on the reduction ratio at the highest concentration: lysophosphatidylglycerol > lysophosphatidylcholine > lysophosphatidyletanolamine > lysophosphatidylserine. In the presence of LPS, only lysophosphatidylinositol (LPI) decreased the IL-8 secretion induced by LPS. Focusing on the G protein-coupled receptors (GPCRs) that LPI acts on, PSN375963 and AS1269574, GPR119 agonists, decreased the IL-8 secretion induced by LPS. It is speculated that IL-8 secretion was reduced by LPI via GPR119 signaling under non-inflammatory conditions. Although the detailed mechanism remains to be elucidated, the findings that LPLs, except for LPI, have inhibitory effects and that LPI has an inhibitory/anti-inflammatory effect on IL-8 secretion will help to elucidate the mechanism on the onset of colonic diseases and the planning of treatment methods in the future.