The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state

Nucleic Acids Research

Volumn 43, Issue 10, 2015, Pages 5033-5051

  Adhikary, Till ^a   Wortmann, Annika ^a   Schumann, Tim ^a   Finkernagel, Florian ^a   Lieber, Sonja ^a   Roth, Katrin ^a   Toth, Philipp M ^a   Diederich, Wibke E ^a   Nist, Andrea ^a   Stiewe, Thorsten ^a   Kleinesudeik, Lara ^a   Reinartz, Silke ^a   Müller Brüsselbach, Sabine ^a   Müller, Rolf ^a  

^a Fachbereich Medizin der Universitat Marburg   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

FC RECEPTOR IIB; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDOLEAMINE 2,3 DIOXYGENASE; INDOLEAMINE 2,3 DIOXYGENASE 1; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 8; KYNURENINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PROGRAMMED DEATH 1 LIGAND 1; STAT1 PROTEIN; UNCLASSIFIED DRUG; TRANSCRIPTOME;

ADULT; ANIMAL CELL; ARTICLE; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL SURVIVAL; CONTROLLED STUDY; GENE REPRESSION; GENE TARGETING; GENETIC CODE; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; HYPOXIA; IMMUNOREGULATION; LYMPHOCYTE ACTIVATION; MACROPHAGE; MONOCYTE; NONHUMAN; NORMAL HUMAN; PHENOTYPE; PRIORITY JOURNAL; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; AGONISTS; CELL CULTURE; CELL DIFFERENTIATION; CELL LINE; CYTOLOGY; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; IMMUNOLOGY; MACROPHAGE ACTIVATION; METABOLISM;

CELL DIFFERENTIATION; CELL LINE; CELLS, CULTURED; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORKS; HUMANS; MACROPHAGE ACTIVATION; MACROPHAGES; MONOCYTES; PPAR DELTA; PPAR-BETA; TRANSCRIPTOME;

EID: 84931052960     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkv331     Document Type: Article

References (70)

1. Sica, A. and Mantovani, A. (2012) Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest., 122, 787-795.
2. Martinez, F.O. and Gordon, S. (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep., 6, 13.
3. Xue, J., Schmidt, S.V., Sander, J., Draffehn, A., Krebs, W., Quester, I., De Nardo, D., Gohel, T.D., Emde, M., Schmidleithner, L. et al. (2014) Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity, 40, 274-288.
4. Kostadinova, R., Wahli, W. and Michalik, L. (2005) PPARs in diseases: control mechanisms of infammation. Curr. Med. Chem., 12, 2995-3009.
5. Yang, Y., Lovett-Racke, A.E. and Racke, M.K. (2010) Regulation of immune responses and autoimmune encephalomyelitis by PPARs. PPAR Res., 2010, 104705.
6. Wahli, W. and Michalik, L. (2012) PPARs at the crossroads of lipid signaling and infammation. Trends Endocrinol. Metab., 23, 351-363.
7. Michalik, L. and Wahli, W. (2008) PPARs mediate lipid signaling in infammation and cancer. PPAR Res., 2008, 134059.
8. Peters, J.M., Lee, S.S., Li, W., Ward, J.M., Gavrilova, O., Everett, C., Reitman, M.L., Hudson, L.D. and Gonzalez, F.J. (2000) Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol. Cell. Biol., 20, 5119-5128.
9. Chong, H.C., Tan, M.J., Philippe, V., Tan, S.H., Tan, C.K., Ku, C.W., Goh, Y.Y., Wahli, W., Michalik, L. and Tan, N.S. (2009) Regulation of epithelial-mesenchymal IL-1 signaling by PPARbeta/delta is essential for skin homeostasis and wound healing. J. Cell Biol., 184, 817-831.
10. Bassaganya-Riera, J., DiGuardo, M., Climent, M., Vives, C., Carbo, A., Jouni, Z.E., Einerhand, A.W., O'Shea, M. and Hontecillas, R. (2011) Activation of PPARgamma and delta by dietary punicic acid ameliorates intestinal infammation in mice. Br. J. Nutr., 106, 878-886.
11. Kanakasabai, S., Chearwae, W., Walline, C.C., Iams, W., Adams, S.M. and Bright, J.J. (2010) Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis. Immunology, 130, 572-588.
12. Kang, K., Reilly, S.M., Karabacak, V., Gangl, M.R., Fitzgerald, K., Hatano, B. and Lee, C.H. (2008) Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab., 7, 485-495.
13. Odegaard, J.I., Ricardo-Gonzalez, R.R., Red Eagle, A., Vats, D., Morel, C.R., Goforth, M.H., Subramanian, V., Mukundan, L., Ferrante, A.W. and Chawla, A. (2008) Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab., 7, 496-507.
14. Westergaard, M., Henningsen, J., Johansen, C., Rasmussen, S., Svendsen, M.L., Jensen, U.B., Schroder, H.D., Staels, B., Iversen, L., Bolund, L. et al. (2003) Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal andlesional psoriatic skin. J. Invest. Dermatol, 121, 1104-1117.
15. Romanowska, M., Reilly, L., Palmer, C.N., Gustafsson, M.C. and Foerster, J. (2010) Activation of PPARbeta/delta causes a psoriasis-like skin disease in vivo. PLoS One, 5, e9701.
16. Hack, K., Reilly, L., Palmer, C, Read, K.D., Norval, S., Kime, R., Booth, K. and Foerster, J. (2012) Skin-targeted inhibition of PPAR beta/delta by selective antagonists to treat PPAR beta/delta-mediated psoriasis-like skin sisease in vivo. PLoS One, 7, e37097.
17. Peters, J.M., Shah, Y.M. and Gonzalez, F.J. (2012) The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat. Rev. Cancer, 12, 181-195.
18. Adhikary, T., Kaddatz, K., Finkernagel, F., Schönbauer, A., Meissner, W., Scharfe, M., Jarek, M., Blöcker, H., Müller-Brüsselbach, S. and Müller, R. (2011) Genomewide analyses defne different modes of transcriptional regulation by peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). PLoS One, 6, e 16344.
19. Adhikary, T., Brandt, D.T., Kaddatz, K., Stockert, J., Naruhn, S., Meissner, W., Finkernagel, F, Obert, J., Lieber, S., Scharfe, M. et al (2013) Inverse PPARbeta/delta agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion. Oncogene, 32, 5241-5252.
20. Planavila, A., Rodriguez-Calvo, R., Jove, M., Michalik, L., Wahli, W., Laguna, J.C. and Vazquez-Carrera, M. (2005) Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes. Cardiovasc. Res., 65, 832-841.
21. Stockert, J., Wolf, A., Kaddatz, K., Schnitzer, E., Finkernagel, F, Meissner, W., Müller-Brüsselbach, S., Kracht, M. and Müller, R. (2013) Regulation of TAK1/TAB1-mediated IL-1beta signaling by cytoplasmic PPARbeta/delta. PLoS One, 8, e63011.
22. Rodriguez-Calvo, R., Serrano, L., Coll, T., Moullan, N., Sanchez, R.M., Merlos, M., Palomer, X., Laguna, J.C, Michalik, L., Wahli, W. et al (2008) Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2. Diabetes, 57, 2149-2157.
23. Lee, C.H., Chawla, A., Urbiztondo, N., Liao, D., Boisvert, W.A., Evans, R.M. and Curtiss, L.K. (2003) Transcriptional repression of atherogenic infammation: modulation by PPARdelta. Science, 302, 453-457.
24. Barish, GD., Yu, R.T, Karunasiri, M., Ocampo, C.B., Dixon, J., Benner, C, Dent, A.L., Tangirala, R.K. and Evans, R.M. (2010) Bcl-6 and NF-kappaB cistromes mediate opposing regulation of the innate immune response. Genes Dev, 24, 2760-2765.
25. Xu, H.E., Lambert, M.H., Montana, V.G, Parks, D.J., Blanchard, S.G, Brown, PJ., Sternbach, D.D., Lehmann, J.M., Wisely, GB., Willson, TM. et al (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell, 3, 397-403.
26. Naruhn, S., Meissner, W., Adhikary, T, Kaddatz, K., Klein, T., Watzer, B., Müller-Brüsselbach, S. and Müller, R. (2010) 15-hydroxyeicosatetraenoic acid is a preferential peroxisome proliferator-activated receptor ß/S agonist. Mol Pharmacol, 77, 171-184.
27. Lim, H., Gupta, R.A., Ma, W.G, Paria, B.C, Moller, D.E., Morrow, J.D., DuBois, R.N., Trzaskos, J.M. and Dey, S.K. (1999) Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev, 13, 1561-1574.
28. Fauti, T, Müller-Brüsselbach, S., Kreutzer, M., Rieck, M., Meissner, W., Rapp, U., Schweer, H., Kömhoff, M. and Müller, R. (2006) Induction of PPARbeta and prostacyclin (PGI2) synthesis by Raf signaling: failure of PGI2 to activate PPARbeta. FEBS J., 273, 170-179.
29. Rao, GH., Reddy, K.R., Hagert, K. and White, J.G (1980) Infuence of pH on the prostacyclin (PGI2) mediated inhibition of platelet function. Prostaglandins Med., 4, 263-273.
30. Billin, A.N. (2008) PPAR-beta/delta agonists for Type 2 diabetes and dyslipidemia: an adopted orphan still looking for a home. Expert Opin. Investig. Drugs, 17, 1465-1471.
31. Peraza, M.A., Burdick, A.D., Marin, H.E., Gonzalez, F.J. and Peters, J.M. (2006) The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR). Toxicol Sci., 90, 269-295.
32. Shearer, B.G., Steger, D.J., Way, J.M., Stanley, T.B., Lobe, D.C., Grillot, D.A., Iannone, M.A., Lazar, M.A., Willson, T.M. and Billin, A.N. (2008) Identifcation and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist. Mol. Endocrinol., 22, 523-529.
33. Naruhn, S., Toth, P.M., Adhikary, T., Kaddatz, K., Pape, V., Dörr, S., Klebe, G., Müller-Brüsselbach, S., Diederich, W.E. and Müller, R. (2011) High-affnity peroxisome proliferator-activated receptor beta/delta-specifc ligands with pure antagonistic or inverse agonistic properties. Mol. Pharmacol., 80, 828-838.
34. Toth, P.M., Naruhn, S., Pape, V.F., Dörr, S.M., Klebe, G., Müller, R. and Diederich, W.E. (2012) Development of improved PPARbeta/delta inhibitors. ChemMedChem, 7, 159-170.
35. Tanaka, T., Tahara-Hanaoka, S., Nabekura, T., Ikeda, K., Jiang, S., Tsutsumi, S., Inagaki, T., Magoori, K., Higurashi, T., Takahashi, H. et al. (2014) PPARbeta/delta activation of CD300a controls intestinal immunity. Sci. Rep., 4, 5412.
36. Lieber, S., Scheer, F., Finkernagel, F., Meissner, W., Giehl, G., Brendel, C., Diederich, W.E., Muller-Brusselbach, S. and Muller, R. (2015) The inverse agonist DG172 triggers a PPARbeta/delta-independent myeloid lineage shift and promotes GM-CSF/IL-4-induced dendritic cell differentiation. Mol. Pharmacol., 87, 162-173.
37. Reinartz, S., Schumann, T., Finkernagel, F., Wortmann, A., Jansen, J.M., Meissner, W., Krause, M., Schworer, A.M., Wagner, U., Muller-Brusselbach, S. et al. (2014) Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: Correlation of CD163 expression, cytokine levels and early relapse. Int. J. Cancer, 134, 32-42.
38. Braun, D., Longman, R.S. and Albert, M.L. (2005) A two-step induction of indoleamine 2, 3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood, 106, 2375-2381.
39. Liao, Y., Smyth, G.K. and Shi, W. (2013) The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res., 41, e108.
40. Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M. and Gingeras, T.R. (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics, 29, 15-21.
41. Satoh, J. and Tabunoki, H. (2013) A comprehensive profle of ChIP-Seq-based STAT1 target genes suggests the complexity of STAT1-mediated gene regulatory mechanisms. Gene Regul. Syst. Bio., 7, 41-56.
42. Hutchins, A.P., Poulain, S. and Miranda-Saavedra, D. (2012) Genome-wide analysis of STAT3 binding in vivo predicts effectors of the anti-infammatory response in macrophages. Blood, 119, e110-e119.
43. Ghisletti, S., Barozzi, I., Mietton, F., Polletti, S., De Santa, F., Venturini, E., Gregory, L., Lonie, L., Chew, A., Wei, C.L. et al. (2010) Identifcation and characterization of enhancers controlling the infammatory gene expression program in macrophages. Immunity, 32, 317-328.
44. Haskill, S., Johnson, C., Eierman, D., Becker, S. and Warren, K. (1988) Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J. Immunol., 140, 1690-1694.
45. Sporn, S.A., Eierman, D.F., Johnson, C.E., Morris, J., Martin, G., Ladner, M. and Haskill, S. (1990) Monocyte adherence results in selective induction of novel genes sharing homology with mediators of infammation and tissue repair. J. Immunol., 144, 4434-4441.
46. Kelley, J.L., Rozek, M.M., Suenram, C.A. and Schwartz, C.J. (1987) Activation of human blood monocytes by adherence to tissue culture plastic surfaces. Exp. Mol. Pathol., 46, 266-278.
47. Fuhlbrigge, R.C., Chaplin, D.D., Kiely, J.M. and Unanue, E.R. (1987) Regulation of interleukin 1 gene expression by adherence and lipopolysaccharide. J. Immunol., 138, 3799-3802.
48. Eierman, D.F., Johnson, C.E. and Haskill, J.S. (1989) Human monocyte infammatory mediator gene expression is selectively regulated by adherence substrates. J. Immunol., 142, 1970-1976.
49. Coccia, E.M., Del Russo, N., Stellacci, E., Testa, U., Marziali, G. and Battistini, A. (1999) STAT1 activation during monocyte to macrophage maturation: role of adhesion molecules. Int. Immunol., 11, 1075-1083.
50. Rosales, C. and Juliano, R. (1996) Integrin signaling to NF-kappa B in monocytic leukemia cells is blocked by activated oncogenes. Cancer Res., 56, 2302-2305.
51. Mandard, S., Zandbergen, F., Tan, N.S., Escher, P., Patsouris, D., Koenig, W., Kleemann, R., Bakker, A., Veenman, F., Wahli, W. et al. (2004) The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofbrate treatment. J. Biol. Chem., 279, 34411-34420.
52. Bours, V., Franzoso, G., Azarenko, V., Park, S., Kanno, T., Brown, K. and Siebenlist, U. (1993) The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers. Cell, 72, 729-739.
53. Palombella, V.J., Rando, O.J., Goldberg, A.L. and Maniatis, T. (1994) The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell, 78, 773-785.
54. Wu, H.M., Wen, H.C. and Lin, W.W. (2002) Proteasome inhibitors stimulate interleukin-8 expression via Ras and apoptosis signal-regulating kinase-dependent extracellular signal-related kinase and c-Jun N-terminal kinase activation. Am. J. Respir. Cell Mol. Biol., 27, 234-243.
55. Munn, D.H. and Mellor, A.L. (2013) Indoleamine 2, 3 dioxygenase and metabolic control of immune responses. Trends Immunol., 34, 137-143.
56. Francisco, L.M., Sage, P.T. and Sharpe, A.H. (2010) The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev., 236, 219-242.
57. Silk, J.D., Salio, M., Brown, J., Jones, E.Y. and Cerundolo, V. (2008) Structural and functional aspects of lipid binding by CD1 molecules. Annu. Rev. Cell Dev. Biol., 24, 369-395.
58. Guilliams, M., Bruhns, P., Saeys, Y., Hammad, H. and Lambrecht, B.N. (2014) The function of Fcgamma receptors in dendritic cells and macrophages. Nat. Rev. Immunol., 14, 94-108.
59. Rival, Y., Beneteau, N., Taillandier, T., Pezet, M., Dupont-Passelaigue, E., Patoiseau, J.F., Junquero, D., Colpaert, F.C. and Delhon, A. (2002) PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells. Eur. J. Pharmacol., 435, 143-151.
60. Ding, G., Cheng, L., Qin, Q., Frontin, S. and Yang, Q. (2006) PPARdelta modulates lipopolysaccharide-induced TNFalpha infammation signaling in cultured cardiomyocytes. J. Mol. Cell. Cardiol., 40, 821-828.
61. Wang, L.H., Yang, X.Y, Zhang, X., Huang, J., Hou, J., Li, J., Xiong, H., Mihalic, K., Zhu, H., Xiao, W. et al. (2004) Transcriptional inactivation of STAT3 by PPARgamma suppresses IL-6-responsive multiple myeloma cells. Immunity, 20, 205-218.
62. Kino, T., Rice, K.C. and Chrousos, G.P. (2007) The PPARdelta agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition. Eur. J. Clin. Invest., 37, 425-433.
63. Serrano-Marco, L., Barroso, E., El Kochairi, I., Palomer, X., Michalik, L., Wahli, W. and Vazquez-Carrera, M. (2011) The peroxisome proliferator-activated receptor (PPAR) beta/delta agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells. Diabetologia, 55, 743-751.
64. Serrano-Marco, L., Rodriguez-Calvo, R., El Kochairi, I., Palomer, X., Michalik, L., Wahli, W. and Vazquez-Carrera, M. (2011) Activation of peroxisome proliferator-activated receptor-beta/-delta (PPAR-beta/-delta) ameliorates insulin signaling and reduces SOCS3 levels by inhibiting STAT3 in interleukin-6-stimulated adipocytes. Diabetes, 60, 1990-1999.
65. Latz, E., Xiao, TS. and Stutz, A. (2013) Activation and regulation of the infammasomes. Nat. Rev. Immunol, 13, 397-411.
66. Wiezlak, M., Diring, J., Abella, J., Mouilleron, S., Way, M., McDonald, N.Q. and Treisman, R. (2012) G-actin regulates the shuttling and PP1 binding of the RPEL protein Phactr1 to control actomyosin assembly. J. Cell Sci., 125, 5860-5872.
67. Singh, K.K., Ge, X., Mao, Y, Drane, L., Meletis, K., Samuels, B.A. and Tsai, L.H. (2010) Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron, 67, 33-48.
68. Xu, Z., Liu, D., Fan, C, Luan, L., Zhang, X. and Wang, E. (2014) DIXDC1 increases the invasion and migration ability of non-small-cell lung cancer cells via the PI3K-AKT/AP-1 pathway. Mol Carcinog., 53, 917-925.
69. Stockert, J., Adhikary, T, Kaddatz, K., Finkernagel, F., Meissner, W., Müller-Brüsselbach, S. and Müller, R. (2011) Reverse crosstalk of TGFß and PPARß/S signaling identifed by transcriptional profling. Nucleic Acids Res., 39, 119-131.
70. Eltzschig, H.K. and Carmeliet, P (2011) Hypoxia and infammation. N. Engl. J. Med., 364, 656-665.