Abstract

Background: Th2-cytokines, such as interleukins-4 and -13 (IL-4, IL-13),have been identified as alternative stimuli of monocytes/macrophages. We have recently profiled the gene-expressionpattern of IL-4-teated human peripheral monocytes and found that 15-lipoxygenase-1 (15-LOX1) and monoamineoxidase A (MAO-A) are among the five most strongly upregulated gene products in IL-4-treated cells. Transfectionof monocytic cells (U937) with 15-LOX1 also induced MAO-A expression. These data suggested that 15-LOX1products might play a role in the IL4-induced signaling cascade leading to expression of MAO-A in humanmonocytes. Material/Methods: To test this hypothesis we incubated wild-type and 15-LOX1-transfected U937cells with different concentrations of either IL-4 or 15-LOX-products [13S-H(p)ODE, 15S-H(p)ETE] andquantified the expression of 15-LOX1, MAO-A, and MAO-B by activity assays and real-time RT-PCR. Results:Wild-type U937 cells express neither MAO-A nor MAO-B, but after three days of IL4 treatment, MAO-A mRNAwas detected. A similar isoform-specific expression of MAO-A mRNA was observed when U937 cells were transfectedwith 15-LOX1 or when the cells were incubated with primary 15-LOX1 products (hydroperoxy fatty acids)or H2O2. In contrast, the corresponding hydroxy fatty acids were ineffective. Conclusions: These dataindicate that increased intracellular peroxide concentrations (oxidative stress) induce MAO-A expressionin monocytes/macrophages, which normally do not express the enzyme. Our findings also suggest that IL-4-inducedupregulation of MAO-A expression in human peripheral monocytes may proceed via 15-LOX1-dependent and15-LOX1-independent pathways. The biological role of MAO-A expression for monocyte function is discussed.

Keywords: Gene Expression Regulation, Enzymologic - genetics, Arachidonate 15-Lipoxygenase - metabolism, Gene Expression Regulation, Enzymologic - genetics, Interleukin-4 - pharmacology, Isoenzymes - metabolism, Linoleic Acid - metabolism, Monoamine Oxidase - metabolism, Monocytes - enzymology, Th2 Cells - metabolism