Monoamine oxidase A (MAO-A) is a mitochondrial flavoen-zyme implicated in the pathogenesis of atherosclerosis and inflammation and also in many neurological disorders. MAO-A also has been reported as a potential therapeutic target in prostate cancer. However, the regulatory mechanisms controlling cytokine-induced MAO-A expression in immune or cancer cells remain to be identified. Here, we show that MAO-A expression is co-induced with 15-lipoxygenase (15-LO) in interleukin 13 (IL-13)-activated primary human monocytes and A549 nonsmall cell lung carcinoma cells. We present evidence that MAO-A gene expression and activity are regulated by signal transducer and activator of transcription 1, 3, and 6 (STAT1, STAT3, and STAT6), early growth response 1 (EGR1), and cAMP-responsive element– binding protein (CREB), the same transcription factors that control IL-13– dependent 15-LO expression. We further established that in both primary monocytes and in A549 cells, IL-13–stimulated MAO-A expression, activity, and function are directly governed by 15-LO. In contrast, IL-13– driven expression and activity of MAO-A was 15-LO–independent in U937 promonocytic cells. Furthermore, we demonstrate that the 15-LO– dependent transcriptional regulation of MAO-A in response to IL-13 stimulation in monocytes and in A549 cells is mediated by peroxisome proliferator–activated receptor (PPAR) and that signal transducer and activator of transcription 6 (STAT6) plays a crucial role in facilitating the transcriptional activity of PPAR. We further report that the IL-13–STAT6 – 15-LO–PPAR axis is critical for MAO-A expression, activity, and function, including migration and reactive oxygen species generation. Altogether, these results have major implications for the resolution of inflammation and indicate
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-11485 |
| Date | 07 September 2018 |
| Creators | Dhabal, Sukhamoy, Das, Pradip, Biswas, Pritam, Kumari, Priyanka, Yakubenko, Valentin P., Kundu, Suman, Cathcart, Martha K., Kundu, Manjari, Biswas, Kaushik, Bhattacharjee, Ashish |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | ETSU Faculty Works |
| Rights | http://creativecommons.org/licenses/by/4.0/ |
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