Regulation of monoamine oxidase A (MAO-A) expression, activity, and function in IL-13–stimulated monocytes and A549 lung carcinoma cells

We show that Monoamine oxidase A expression is co-induced with 15-lipoxygenase in interleukin 13 -activated primary human monocytes and A549 nonsmall cell lung carcinoma cells

Sukhamoy Dhabal; Pradip Das; Pritam Biswas; Priyanka Kumari; Valentin P. Yakubenko; Suman Kundu; Martha K. Cathcart; Manjari Kundu; Kaushik Biswas; Ashish Bhattacharjee

2018

Scholarcy highlights

  • Monoamine oxidase A is a mitochondrial flavoenzyme implicated in the pathogenesis of atherosclerosis and inflammation and in many neurological disorders
  • We demonstrate that the 15-LO– dependent transcriptional regulation of MAO-A in response to interleukin 13 stimulation in monocytes and in A549 cells is mediated by peroxisome proliferator–activated receptor ␥ and that signal transducer and activator of transcription 6 plays a crucial role in facilitating the transcriptional activity of PPAR␥
  • We demonstrated that during IL-13 stimulation 15-lipoxygenase and MAO-A are the two strongly up-regulated genes that are co-induced in primary monocytes/macrophages, A549 lung carcinoma cells, and in normal human bronchial epithelial cells
  • Considering the role of MAO-A in the resolution of inflammation and its other pathophysiological implications, it is an extremely important requirement to carry out a detailed investigation to understand the regulatory mechanisms associated with the expression and function of MAO-A during IL-13 activation of primary monocyte/macrophages, A549 lung carcinoma cells, and in U937 promonocytic cells, which is the primary focus of this study
  • The outcome of this study, shows that IL-13 induction of MAO-A has a major contribution in the resolution of inflammation and in enhancement of the metastatic potential of cancer cells
  • The discrepancies between the observations in H1299, NSCLC, HCT116, and PC3 cells on the one hand and in A549 and NHBE cells on the other hand can be explained by the fact that in H1299, HCT116, or in PC3 cells, the relative expression level of the decoy receptor is probably very high compared with the IL-13R␣1 component that may affect the normal IL-13 signaling
  • These data strongly suggest that interleukin 13 signal transduction uses a distinct 15-LO and PPAR␥-dependent mechanism that is regulated by Stat6 in A549 cells and in primary monocytes/macrophages to control the IL-13– driven function of Monoamine oxidase A in tyramine-induced reactive oxygen species generation

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