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Cytokine-Dependent Expression Regulation of ALOX15

Hartmut Kuhn, Tatjana Gehring, Andrea Schröter and Dagmar Heydeck

Lipoxygenases (LOX) are lipid-peroxidizing enzymes that play a role in cell differentiation, but have also been implicated in the pathogenesis of inflammatory, hyperproliferative and neurological disorders. They are widely distributed in plants and mammals but also occur sporadically in lower organisms. The human genome involves six functional LOX genes and a corrupted pseudogene. 20 years ago it was reported that expression of ALOX15 was specifically induced in human peripheral monocytes by the classical Th2 cytokine interleukin 4 and later expression array profiles indicated that this enzyme is the most strongly upregulated gene product in human monocytes. Although the molecular basis for this IL4-dependent expression regulation has extensively been studied during the past 20 years, there are still a number of unsolved questions. This review is aimed at summarizing the current knowledge on the cytokine-dependent expression regulation of ALOX15 with particular focus on the Th2 cytokines interleukin-4 and interleukin-13 in various cells and tissues and at critically evaluating the potential biological implication of this effect.