Endogenous eicosanoids modulate cell growth and the expression of immediate early response genes.

Experiments were performed in rat mesangial cells indicating that endogenous non-cyclooxygenase metabolites of AA act to modulate the mitogenic response. Irrespective of the mitogen used, metabolism of AA by LO and/or CP 450 influences induction of cell growth and expression of the immediate early response genes c-fos and Egr-1. In accordance with other reports (3,4) on the influence of eicosanoids on gene expression, our observations indicate that endogenous eicosanoids may act as intracellular mediators. In the mitogenic response, at least two mechanisms of modulation seem possible: i) AA and its metabolites may act by modulating other 2nd messenger systems or ii) eicosanoids may directly regulate the expression of growth-related genes, e.g. by interacting with a fatty acid response element in the promoter region of respective genes.