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

Monocytes/macrophages are versatile cells centrally involved in host defense and immunity. Th1 cytokines induce a classical activation program in monocytes/macrophages leading to a proinflammatory M1 macrophage phenotype while Th2 cytokines IL-4 and IL-13 promote monocyte differentiation into an alternatively activated, anti-inflammatory M2 macrophage phenotype. Although monoamine oxidase A (MAO-A) is primarily known for its action in the nervous system, several recent studies have identified MAO-A as a signature marker of alternative activation of monocytes/macrophages. In this brief review we explore the signaling pathways/molecules that regulate MAO-A expression in alternatively activated monocytes/macrophages. We further discuss the contribution of MAO-A to the resolution of inflammation and identify potential therapeutic targets for controlling inflammation. Altogether this review provides deeper insight into the role of MAO-A in alternative activation of monocytes/macrophages and their participation in the inflammatory response.

[1]  Dipali A. Date,et al.  Kruppel-like Transcription Factor 6 Regulates Inflammatory Macrophage Polarization* , 2014, The Journal of Biological Chemistry.

[2]  T. Schwartz A neuroscientific update on monoamine oxidase and its inhibitors , 2013, CNS Spectrums.

[3]  L. Nagy,et al.  Identification of novel markers of alternative activation and potential endogenous PPARγ ligand production mechanisms in human IL-4 stimulated differentiating macrophages. , 2012, Immunobiology.

[4]  M. Cathcart,et al.  From Macrophage Interleukin-13 Receptor to Foam Cell Formation , 2012, Journal of Biological Chemistry.

[5]  V. Vaccarino,et al.  MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample , 2012, BMC Medical Genetics.

[6]  Xiao‐Yu Yin,et al.  Monoamine oxidase A expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events , 2012, Laboratory Investigation.

[7]  L. Nagy,et al.  Nuclear hormone receptors enable macrophages and dendritic cells to sense their lipid environment and shape their immune response. , 2012, Physiological reviews.

[8]  G. Feldman,et al.  Hck Is a Key Regulator of Gene Expression in Alternatively Activated Human Monocytes* , 2011, The Journal of Biological Chemistry.

[9]  L. Nagy,et al.  PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation☆ , 2011, Biochimica et biophysica acta.

[10]  K. Clément,et al.  Krüppel-like factor 4 regulates macrophage polarization. , 2011, The Journal of clinical investigation.

[11]  Roberta Menabò,et al.  Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. , 2011, Biochimica et biophysica acta.

[12]  C. Ufer,et al.  Monoamine Oxidase A Expression Is Vital for Embryonic Brain Development by Modulating Developmental Apoptosis* , 2011, The Journal of Biological Chemistry.

[13]  M. Cathcart,et al.  &agr;M&bgr;2 Integrin Activation Prevents Alternative Activation of Human and Murine Macrophages and Impedes Foam Cell Formation , 2011, Circulation research.

[14]  R. Evans,et al.  STAT6 Transcription Factor Is a Facilitator of the Nuclear Receptor PPARγ-Regulated Gene Expression in Macrophages and Dendritic Cells , 2010, Immunity.

[15]  R. Martinez-Nunez,et al.  The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor α1 (IL13Rα1)* , 2010, The Journal of Biological Chemistry.

[16]  G. Feldman,et al.  Monocyte 15-Lipoxygenase Gene Expression Requires ERK1/2 MAPK Activity , 2010, The Journal of Immunology.

[17]  K. Morikawa,et al.  The nuclear receptor PPARγ individually responds to serotonin‐ and fatty acid‐metabolites , 2010, The EMBO journal.

[18]  A. Ryan,et al.  Rac1-mediated Mitochondrial H2O2 Generation Regulates MMP-9 Gene Expression in Macrophages via Inhibition of SP-1 and AP-1* , 2010, The Journal of Biological Chemistry.

[19]  S. Gordon,et al.  Alternative activation of macrophages: mechanism and functions. , 2010, Immunity.

[20]  Susan R. Quinn,et al.  IL-10 Inhibits miR-155 Induction by Toll-like Receptors* , 2010, The Journal of Biological Chemistry.

[21]  S. Gordon,et al.  Alternative activation of macrophages: an immunologic functional perspective. , 2009, Annual review of immunology.

[22]  Hana Lee,et al.  Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. , 2009, Immunity.

[23]  W. Paul,et al.  Type I IL-4Rs Selectively Activate IRS-2 to Induce Target Gene Expression in Macrophages , 2008, Science Signaling.

[24]  J. Edwards,et al.  Exploring the full spectrum of macrophage activation , 2008, Nature Reviews Immunology.

[25]  K. Christopher Garcia,et al.  Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 System , 2008, Cell.

[26]  S. Haulon,et al.  PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. , 2007, Cell metabolism.

[27]  S. Itohara,et al.  MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2, and the sphingolipid pathway. , 2007, Free radical biology & medicine.

[28]  Frank Brombacher,et al.  Macrophage-specific PPARγ controls alternative activation and improves insulin resistance , 2007, Nature.

[29]  J. Auwerx,et al.  IL‐13 induces expression of CD36 in human monocytes through PPARγ activation , 2007, European journal of immunology.

[30]  David Baltimore,et al.  MicroRNA-155 is induced during the macrophage inflammatory response , 2007, Proceedings of the National Academy of Sciences.

[31]  O. Kunduzova,et al.  Oxidative Stress–Dependent Sphingosine Kinase-1 Inhibition Mediates Monoamine Oxidase A–Associated Cardiac Cell Apoptosis , 2007, Circulation research.

[32]  Alberto Mantovani,et al.  Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression1 , 2006, The Journal of Immunology.

[33]  Sylvain Houle,et al.  Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. , 2006, Archives of general psychiatry.

[34]  G. Feldman,et al.  Monocyte 15-Lipoxygenase Expression Is Regulated by a Novel Cytosolic Signaling Complex with Protein Kinase C δ and Tyrosine-Phosphorylated Stat31 , 2006, The Journal of Immunology.

[35]  X. Ou,et al.  Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[36]  S. Ghousunnissa,et al.  Hydrogen peroxide inhibits IL-12 p40 induction in macrophages by inhibiting c-rel translocation to the nucleus through activation of calmodulin protein. , 2006, Blood.

[37]  E. Masini,et al.  Oxidative Stress by Monoamine Oxidase Mediates Receptor-Independent Cardiomyocyte Apoptosis by Serotonin and Postischemic Myocardial Injury , 2005, Circulation.

[38]  H. Kuhn,et al.  Expression regulation of MAO isoforms in monocytic cells in response to Th2 cytokines. , 2005, Medical science monitor : international medical journal of experimental and clinical research.

[39]  V. O’Donnell,et al.  Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and -13. , 2005, Cytokine.

[40]  Silvano Sozzani,et al.  The chemokine system in diverse forms of macrophage activation and polarization. , 2004, Trends in immunology.

[41]  N. Scrutton Chemical aspects of amine oxidation by flavoprotein enzymes. , 2004, Natural product reports.

[42]  J. Fitzgerald,et al.  Th2 Response of Human Peripheral Monocytes Involves Isoform-Specific Induction of Monoamine Oxidase-A12 , 2004, The Journal of Immunology.

[43]  R. El Bekay,et al.  A new role for monoamine oxidases in the modulation of macrophage‐inducible nitric oxide synthase gene expression , 2004, Journal of leukocyte biology.

[44]  G. Feldman,et al.  Role of Protein Kinase C Isoforms in the Regulation of Interleukin-13-induced 15-Lipoxygenase Gene Expression in Human Monocytes* , 2004, Journal of Biological Chemistry.

[45]  G. Feldman,et al.  Interleukin-13 Induction of 15-Lipoxygenase Gene Expression Requires p38 Mitogen-Activated Protein Kinase-Mediated Serine 727 Phosphorylation of Stat1 and Stat3 , 2003, Molecular and Cellular Biology.

[46]  R. Gallego,et al.  Serotonin upregulates the activity of phagocytosis through 5‐HT1A receptors , 2003, British journal of pharmacology.

[47]  M. Cathcart,et al.  IL‐13 signal transduction in human monocytes: phosphorylation of receptor components, association with Jaks, and phosphorylation/activation of Stats , 2002, Journal of leukocyte biology.

[48]  R. Pichler,et al.  Pro-inflammatory role of serotonin and interleukin-6 in arthritis and spondyloarthropathies - measurement of disease activity by bone scan and effect of steroids , 2002, Scandinavian journal of rheumatology.

[49]  D. Granger,et al.  Adhesion molecules and their role in vascular disease. , 2001, American journal of hypertension.

[50]  S. Goerdt,et al.  Alternatively Activated Macrophages Differentially Express Fibronectin and Its Splice Variants and the Extracellular Matrix Protein βIG‐H3 , 2001, Scandinavian journal of immunology.

[51]  D. Conrad,et al.  Regulation of human 12/15-lipoxygenase by Stat6-dependent transcription. , 2000, American journal of respiratory cell and molecular biology.

[52]  T. Willson,et al.  Interleukin-4-dependent production of PPAR-γ ligands in macrophages by 12/15-lipoxygenase , 1999, Nature.

[53]  K. Lesch,et al.  Role of Serotonin in the Immune System and in Neuroimmune Interactions , 1998, Brain, Behavior, and Immunity.

[54]  J. Ihle,et al.  Interleukin-4 and -13 induce upregulation of the murine macrophage 12/15-lipoxygenase activity: evidence for the involvement of transcription factor STAT6. , 1998, Blood.

[55]  J. Wouters,et al.  Structural aspects of monoamine oxidase and its reversible inhibition. , 1998, Current medicinal chemistry.

[56]  B. Brown,et al.  A 70-kDa protein facilitates interleukin-4 signal transduction in the absence of the common gamma receptor chain. , 1997, Biochemical and biophysical research communications.

[57]  O. Silvennoinen,et al.  Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits. , 1994, Science.

[58]  J. Morrow,et al.  Induction of 15-lipoxygenase by interleukin-13 in human blood monocytes. , 1994, The Journal of biological chemistry.

[59]  G. Panagiotidis,et al.  Glucose modulation of islet monoamine oxidase activity in lean and obese hyperglycemic mice. , 1993, Metabolism: clinical and experimental.

[60]  M. Nelen,et al.  Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. , 1993, Science.

[61]  A. Bradley,et al.  Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. , 1993, Science.

[62]  S. Kundu,et al.  IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes/macrophages. , 2013, Free radical biology & medicine.

[63]  Y. Akao,et al.  Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading to cell death or neuroprotection. , 2006, Journal of neural transmission. Supplementum.

[64]  H. Parvez,et al.  The effect of diabetes mellitus on the morphology and physiology of monoamine oxidase in the pancreas. , 2004, Neurotoxicology.

[65]  S. Gordon Alternative activation of macrophages , 2003, Nature Reviews Immunology.

[66]  Medvedev Ae,et al.  Different sensitivity of mitochondrial and cytosolic monoamine oxidases to in vivo but not in vitro inhibition by specific irreversible inhibitors. , 2001 .

[67]  J. Shih,et al.  Role of MAO A and B in neurotransmitter metabolism and behavior. , 1999, Polish journal of pharmacology.

[68]  H. Kuhn,et al.  Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase. , 1992, Proceedings of the National Academy of Sciences of the United States of America.