PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation

Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9–PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.

[1]  R. Prim Shortest connection networks and some generalizations , 1957 .

[2]  A. Barabasi,et al.  Network medicine : a network-based approach to human disease , 2010 .

[3]  C. Glass,et al.  Inflammation and lipid signaling in the etiology of insulin resistance. , 2012, Cell metabolism.

[4]  M. Makuuchi,et al.  Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis , 2002, Nature Medicine.

[5]  B. Nunn,et al.  Tandem mass spectrometry investigation of ADP-ribosylated kemptide , 2009, Journal of the American Society for Mass Spectrometry.

[6]  Elena Aikawa,et al.  Cystathionine &ggr;-lyase Accelerates Osteoclast Differentiation: Identification of a Novel Regulator of Osteoclastogenesis by Proteomic Analysis , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[7]  D. Mozaffarian,et al.  Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. , 2010, Circulation.

[8]  A. Barabasi,et al.  Uncovering disease-disease relationships through the incomplete interactome , 2015, Science.

[9]  J. Aster,et al.  Notch ligand Delta-like 4 blockade attenuates atherosclerosis and metabolic disorders , 2012, Proceedings of the National Academy of Sciences.

[10]  P. Robinson,et al.  Walking the interactome for prioritization of candidate disease genes. , 2008, American journal of human genetics.

[11]  H. Nishimatsu,et al.  Endothelial nitric oxide synthase is essential for the HMG‐CoA reductase inhibitor cerivastatin to promote collateral growth in response to ischemia , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  P. Blackshear,et al.  PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression. , 2014, Blood.

[13]  Bernhard Lüscher,et al.  Expanding functions of intracellular resident mono‐ADP‐ribosylation in cell physiology , 2013, The FEBS journal.

[14]  S. Gordon,et al.  Diversity and plasticity of mononuclear phagocytes , 2011, European journal of immunology.

[15]  S. Goerdt,et al.  Macrophage activation and polarization: nomenclature and experimental guidelines. , 2014, Immunity.

[16]  P. Libby,et al.  An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro , 2001, Circulation.

[17]  J. Yates,et al.  An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database , 1994, Journal of the American Society for Mass Spectrometry.

[18]  R. Singer,et al.  Transcriptional Pulsing of a Developmental Gene , 2006, Current Biology.

[19]  山本 高司,et al.  Dynamic balance とその訓練効果 , 1978 .

[20]  D. Hochstrasser,et al.  Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags. , 2008, Analytical chemistry.

[21]  S. Goenka,et al.  Poly (ADP-ribose) polymerase 14 and its enzyme activity regulates T(H)2 differentiation and allergic airway disease. , 2013, The Journal of allergy and clinical immunology.

[22]  A. Mead,et al.  Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate , 2014, The Journal of experimental medicine.

[23]  X. Rabasseda,et al.  A report from the American Heart Association Scientific Sessions 2012 (November 3-7 - Los Angeles, California, USA). , 2013, Drugs of today.

[24]  L. Paša-Tolić,et al.  Evaluation of SDS depletion using an affinity spin column and IMS‐MS detection , 2012, Proteomics.

[25]  A. Tall,et al.  The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis , 2007, Circulation research.

[26]  K. Ley,et al.  Myeloid cells in atherosclerosis: a delicate balance of anti-inflammatory and proinflammatory mechanisms , 2013, Current opinion in lipidology.

[27]  P. Willey Institutional Animal Care and Use Committee , 2013, Definitions.

[28]  C. Murray,et al.  The Global Burden of Ischemic Heart Disease in 1990 and 2010: The Global Burden of Disease 2010 Study , 2014, Circulation.

[29]  M. Boothby,et al.  Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Alberto Mantovani,et al.  Orchestration of metabolism by macrophages. , 2012, Cell metabolism.

[31]  Peter Libby,et al.  The forgotten majority: unfinished business in cardiovascular risk reduction. , 2005, Journal of the American College of Cardiology.

[32]  Paul M Ridker,et al.  Anti-inflammatory therapies for cardiovascular disease. , 2014, European heart journal.

[33]  Steven P Gygi,et al.  Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry , 2007, Nature Methods.

[34]  Klaus Ley,et al.  Monocyte and macrophage dynamics during atherogenesis. , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[35]  S. Goenka,et al.  PARP-14 Functions as a Transcriptional Switch for Stat6-dependent Gene Activation* , 2010, The Journal of Biological Chemistry.

[36]  K. Fujiu,et al.  Bone Marrow–Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages , 2009, Circulation.

[37]  Rand R. Wilcox Winsorized Robust Measures , 2005 .

[38]  D. Engelke,et al.  Effective expression of small interfering RNA in human cells , 2002, Nature Biotechnology.

[39]  S. Tangye,et al.  Inflammatory Mechanisms in Obesity , 2013 .

[40]  E. Haralambieva,et al.  BAL1/ARTD9 represses the anti-proliferative and pro-apoptotic IFN&ggr;–STAT1–IRF1–p53 axis in diffuse large B-cell lymphoma , 2013, Journal of Cell Science.

[41]  K. Moore,et al.  Macrophages in atherosclerosis: a dynamic balance , 2013, Nature Reviews Immunology.

[42]  Christopher K. Glass,et al.  Atherosclerosis The Road Ahead , 2001, Cell.

[43]  G. Randolph Mechanisms that regulate macrophage burden in atherosclerosis. , 2014, Circulation research.

[44]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.

[45]  G. Natoli,et al.  Transcriptional regulation of macrophage polarization: enabling diversity with identity , 2011, Nature Reviews Immunology.

[46]  Paul E. Black,et al.  Dictionary of Algorithms and Data Structures | NIST , 1998 .

[47]  T. Hirano,et al.  Inflammation amplifier, a new paradigm in cancer biology. , 2014, Cancer research.

[48]  P. Libby,et al.  The vulnerable atherosclerotic plaque: pathogenesis and therapeutic approach. , 2004, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[49]  E. Marcotte,et al.  Prioritizing candidate disease genes by network-based boosting of genome-wide association data. , 2011, Genome research.

[50]  H. Bluyssen,et al.  STAT1 as a central mediator of IFNγ and TLR4 signal integration in vascular dysfunction , 2012, JAK-STAT.

[51]  William Stafford Noble,et al.  Assigning significance to peptides identified by tandem mass spectrometry using decoy databases. , 2008, Journal of proteome research.

[52]  Adrian E. Raftery,et al.  Model-Based Clustering, Discriminant Analysis, and Density Estimation , 2002 .

[53]  G. Fredman,et al.  Common Therapeutic Targets in Cardiometabolic Disease , 2014, Science Translational Medicine.

[54]  Matthew Brook,et al.  Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Regulates Tumor Necrosis Factor mRNA Stability and Translation Mainly by Altering Tristetraprolin Expression, Stability, and Binding to Adenine/Uridine-Rich Element , 2006, Molecular and Cellular Biology.

[55]  Hiroshi Iwata,et al.  mIMT-visHTS: A novel method for multiplexing isobaric mass tagged datasets with an accompanying visualization high throughput screening tool for protein profiling. , 2015, Journal of proteomics.

[56]  A. Barabasi,et al.  A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes in asthma. , 2015, Human molecular genetics.

[57]  R. Lahesmaa,et al.  PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells. , 2009, Blood.

[58]  O. McGuinness,et al.  Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family , 2011, Proceedings of the National Academy of Sciences.

[59]  I. Tabas Macrophage death and defective inflammation resolution in atherosclerosis , 2010, Nature Reviews Immunology.

[60]  C. Mueller-Dieckmann,et al.  Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases. , 2008, Frontiers in bioscience : a journal and virtual library.

[61]  P. Libby,et al.  Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites , 2009, Science.

[62]  D. Mozaffarian,et al.  Heart disease and stroke statistics--2010 update: a report from the American Heart Association. , 2010, Circulation.

[63]  A. Duschl,et al.  STAT6-dependent and -independent mechanisms in Th2 polarization , 2012, European journal of immunology.

[64]  M. Nahrendorf,et al.  Leukocyte Behavior in Atherosclerosis, Myocardial Infarction, and Heart Failure , 2013, Science.

[65]  R. Aguiar,et al.  B-aggressive Lymphoma Family Proteins Have Unique Domains That Modulate Transcription and Exhibit Poly(ADP-ribose) Polymerase Activity* , 2005, Journal of Biological Chemistry.

[66]  Ullrich Köthe,et al.  Computational protein profile similarity screening for quantitative mass spectrometry experiments , 2010, Bioinform..

[67]  T. Vos,et al.  The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study , 2014, Annals of the rheumatic diseases.