Lysophosphatidylcholine (lysoPC) is generated by the action of phospholipase A2 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 non-toxic 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.