Expression regulation of MAO isoforms in monocytic cells in response to Th2 cytokines

CHAITIDIS, P., BILLETT, E., KUBAN, R.J., UNGETHUEM, U. and KUHN, H., 2005. Expression regulation of MAO isoforms in monocytic cells in response to Th2 cytokines. Medical Science Monitor, 11 (8). ISSN 1234-1010

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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-expression pattern of IL-4-teated human peripheral monocytes and found that 15-lipoxygenase-1 (15-LOX1) and monoamine oxidase A (MAO-A) are among the five most strongly upregulated gene products in IL-4-treated cells. Transfection of monocytic cells (U937) with 15-LOX1 also induced MAO-A expression. These data suggested that 15-LOX1 products might play a role in the IL4-induced signaling cascade leading to expression of MAO-A in human monocytes. Material/Methods: To test this hypothesis we incubated wild-type and 15-LOX1-transfected U937 cells with different concentrations of either IL-4 or 15-LOX-products [13S-H(p)ODE, 15S-H(p)ETE] and quantified 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 mRNA was detected. A similar isoform-specific expression of MAO-A mRNA was observed when U937 cells were transfected with 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 data indicate that increased intracellular peroxide concentrations (oxidative stress) induce MAO-A expression in monocytes/macrophages, which normally do not express the enzyme. Our findings also suggest that IL-4-induced upregulation of MAO-A expression in human peripheral monocytes may proceed via 15-LOX1-dependent and 15-LOX1-independent pathways. The biological role of MAO-A expression for monocyte function is discussed.

Item Type: Journal article
Publication Title: Medical Science Monitor
Creators: Chaitidis, P., Billett, E., Kuban, R.J., Ungethuem, U. and Kuhn, H.
Publisher: Medical Science International
Place of Publication: Albertson, N.Y.
Date: 2005
Volume: 11
Number: 8
ISSN: 1234-1010
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 10:49
Last Modified: 09 Jun 2017 13:40

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