Lysophosphatidylcholine induces keratinocyte differentiation and upregulation of AP-1- and NF-κB DNA-binding activity

Lysophosphatidylcholine ( lysoPC) is generated by the action of phospholipase A(2) on membrane phosphatidylcholine, the most abundant cellular phospholipid. In vitro, lysoPC has pro-inflammatory properties, as it upregulates the expression of adhesion molecules and is a chemoattractant to monocytes and T lymphocytes. It upregulates the expression of a variety of genes including genes encoding growth factors and cyclooxygenase-2 and modulates other cellular responses like proliferation and differentiation. A role for lysoPC as an intracellular messenger transducing signals from membrane-associated receptors has also been suggested. However, the mechanisms behind the diverse actions of lysoPC are poorly understood. In this study we found that lysoPC in nontoxic concentrations caused increased activator protein-1 (AP-1) DNA-binding activity and transglutaminase-1 expression in cultured human keratinocytes. The effects on transglutaminase-1 and AP-1 were dependent on protein kinase C and mitogen-activated protein kinase kinase. In addition, lysoPC caused a rapid and transient increase in DNA-binding activity of nuclear factor-kappaB.