Th2 Response of Human Peripheral Monocytes Involves Isoform-Specific Induction of Monoamine Oxidase-A

Abstract

Monocyte/macrophage function is critically regulated by specific cytokines and growth factors that they are exposed to at inflammatory sites. IL-4 and IL-13 are multifunctional cytokines generated mainly by Th2 lymphocytes that have important biological activities in allergy and inflammation. The Th2 response of human peripheral monocytes is characterized by complex alterations in the gene expression pattern, which involves dominant expression of CD23 cell surface Ag and lipid-peroxidizing 15-lipoxygenase-1 (15-LOX1). In this study, we report that the classical Th2 cytokines IL-4 and IL-13 strongly up-regulate expression of monoamine oxidase A (MAO-A) with no induction of the closely related isozyme, MAO-B. Real-time PCR indicated a >2000-fold up-regulation of the MAO-A transcripts, and immunohistochemistry revealed coexpression of the enzyme with 15-LOX1 in a major subpopulation of monocytes. MAO-A was also induced in lung carcinoma A549 cells by IL-4 in parallel with 15-LOX1. In promyelomonocytic U937 cells, which neither express 15-LOX1 nor MAO-A in response to IL-4 stimulation, expression of MAO-A was up-regulated following transfection with 15-LOX1. This is the first report indicating expression of MAO-A in human monocytes. Its isoform-specific up-regulation in response to Th2 cytokines suggests involvement of the enzyme in modulation of innate and/or acquired immune system.

Genome-wide Profiling of Interleukin-4 and STAT6 Transcription Factor Regulation of Human Th2 Cell Programming

“…In addition, few of the genes, such as MAOA, are suggested to be regulated by STAT6 by using indirect methods such as in silico predictions (Chaitidis et al, 2004). Of the target genes having the largest, over 2-fold, STAT6 knockdown effects in our study (Figure 2A), only six, namely GATA3, GIMAP4, IL24, LTB, SOCS1, and SPINT2, were among the genes identified in the previous studies.…”

Hck Is a Key Regulator of Gene Expression in Alternatively Activated Human Monocytes

“…Using the same Hck-specific antisense ODN, we further checked whether Hck had any effect in regulation of other markers of alternative activation like CD36 (36,44,45) or MAO-A (2,46,47). Our quantitative real-time PCR experiment data showed that the levels of both CD36 and MAO-A mRNA are up-regulated after IL-13 stimulation (Fig.…”

“…Although it is difficult to establish a consensus set of markers for alternative activation of monocytes/macrophages in humans, genes that are regulated by IL-4 and IL-13 include mannose receptor (MR) (36,44), Alox 15 (encodes 12/15-lipoxygenase) (3,4,47), MAO-A (46,47), CD36 (36,44,45), and FN1 (44, 47) among others. Our results demonstrate the important role of Hck in modulating the expression of the MR, a well established, universal marker of alternative activation.…”

Monoamine oxidase A (MAO-A): a signature marker of alternatively activated monocytes/macrophages

“…Although MAO-A expression is strongly upregulated in alternatively activated monocytes/macrophages [9, 10, 12, 14, 58] , the biological importance of MAO-A for monocyte physiology has not been determined. In peripheral tissues, MAO-A is involved in the oxidative catabolism of biogenic amines thereby preventing those amines from entering the circulation.…”