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

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Chaitidis, P., Billett, E. ORCID: 0000-0001-8245-6519, 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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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-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
Record created by:	EPrints Services
Date Added:	09 Oct 2015 10:49
Last Modified:	09 Jun 2017 13:40
URI:	https://irep.ntu.ac.uk/id/eprint/18567