Lysophosphatidylcholine induces keratinocyte differentiation and upregulation of AP-1- and NF-kappaB DNA-binding activity.
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.
Ryborg
Ane Kaltoft
AK
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark. ane@dadlnet.dk
Johansen
Claus
C
Iversen
Lars
L
Kragballe
Knud
K
D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D004268:DNA-Binding Proteins; D008244:Lysophosphatidylcholines; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D011503:Transglutaminases; C105804:transglutaminase 1