Characterization of the promoter and the transcriptional regulation of the lipoxin A4 receptor (FPR2/ALX) gene in human monocytes and macrophages

Journal of Immunology

Volumn 188, Issue 4, 2012, Pages 1856-1867

  Waechter, Vanessa ^a,b   Schmid, Mattia ^a,b   Herova, Magdalena ^a,b   Weber, Angelika ^a,b   Günther, Viola ^b   Marti Jaun, Jacqueline ^a,b   Wüst, Sophia ^a,b   Rösinger, Marian ^a,b   Gemperle, Claudio ^a,b   Hersberger, Martin ^a,b  

^a UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

^b UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

FORMYLPEPTIDE RECEPTOR LIKE 1; GAMMA INTERFERON; INTERFERON REGULATORY FACTOR 1; MESSENGER RNA; OCTAMER TRANSCRIPTION FACTOR 1; TRANSCRIPTION FACTOR SP1;

5' UNTRANSLATED REGION; ALX GENE; ARTICLE; BINDING AFFINITY; BINDING SITE; CELL ACTIVATION; CELL DIFFERENTIATION; CHEMOTAXIS; CONTROLLED STUDY; DOWN REGULATION; EXON; FPR2 GENE; GENE; GENE EXPRESSION; GENE FUNCTION; HUMAN; HUMAN CELL; MACROPHAGE; MONOCYTE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; TRANSCRIPTION REGULATION; UPREGULATION;

5' UNTRANSLATED REGIONS; BINDING SITES; CHEMOTAXIS, LEUKOCYTE; GENE EXPRESSION REGULATION; HUMANS; INTERFERON REGULATORY FACTOR-1; INTERFERON-GAMMA; LIPOPOLYSACCHARIDES; MACROPHAGES; MOLECULAR SEQUENCE DATA; MONOCYTES; ORGANIC CATION TRANSPORTER 1; PROMOTER REGIONS, GENETIC; RECEPTORS, FORMYL PEPTIDE; RECEPTORS, LIPOXIN; REGULATORY SEQUENCES, NUCLEIC ACID; RNA, MESSENGER; SP1 TRANSCRIPTION FACTOR; TRANSCRIPTION INITIATION SITE; TRANSCRIPTION, GENETIC; TRANSCRIPTIONAL ACTIVATION;

EID: 84856911522     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1101788     Document Type: Article

References (72)

1. Serhan, C. N. 1997. Lipoxins and novel aspirin-triggered 15-epi-lipoxins (ATL): a jungle of cell-cell interactions or a therapeutic opportunity? Prostaglandins 53: 107-137. (Pubitemid 27171542)
2. Ye, R. D., F. Boulay, J. M. Wang, C. Dahlgren, C. Gerard, M. Parmentier, C. N. Serhan, and P. M. Murphy. 2009. International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol. Rev. 61: 119-161.
3. Su, S. B., W. Gong, J. L. Gao, W. Shen, P. M. Murphy, J. J. Oppenheim, and J. M. Wang. 1999. A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells. J. Exp. Med. 189: 395-402. (Pubitemid 29063260)
4. He, R., H. Sang, and R. D. Ye. 2003. Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. Blood 101: 1572-1581. (Pubitemid 36182537)
5. Lee, H. Y., M. K. Kim, K. S. Park, Y. H. Bae, J. Yun, J. I. Park, J. Y. Kwak, and Y. S. Bae. 2005. Serum amyloid A stimulates matrix-metalloproteinase-9 upregulation via formyl peptide receptor like-1-mediated signaling in human monocytic cells. Biochem. Biophys. Res. Commun. 330: 989-998. (Pubitemid 40462183)
6. Lee, H. Y., S.D. Kim, J.W. Shim, S.Y. Lee, H. Lee, K. H. Cho, J. Yun, and Y. S. Bae. 2008. Serum amyloid A induces CCL2 production via formyl peptide receptor-like 1-mediated signaling in human monocytes. J. Immunol. 181: 4332-4339.
7. Miao, Z., B. A. Premack, Z. Wei, Y. Wang, C. Gerard, H. Showell, M. Howard, T. J. Schall, and R. Berahovich. 2007. Proinflammatory proteases liberate a discrete high-affinity functional FPRL1 (CCR12) ligand from CCL23. J. Immunol. 178: 7395-7404. (Pubitemid 46847467)
8. Betten, A, J. Bylund, T. Christophe, F. Boulay, A. Romero, K. Hellstrand, and C. Dahlgren. 2001. A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis. J. Clin. Invest. 108: 1221-1228. (Pubitemid 32995381)
9. Schepetkin, I. A., L. N. Kirpotina, J. Tian, A. I. Khlebnikov, R. D. Ye, and M. T. Quinn. 2008. Identification of novel formyl peptide receptor-like 1 agonists that induce macrophage tumor necrosis factor alpha production. Mol. Pharmacol. 74: 392-402.
10. Svensson, L., C. Dahlgren, and C. Wennera° s. 2002. The chemoattractant Trp-Lys- Tyr-Met-Val-D-Met activates eosinophils through the formyl peptide receptor and one of its homologues, formyl peptide receptor-like 1. J. Leukoc. Biol. 72: 810-818. (Pubitemid 36277853)
11. Hu, J. Y., Y. Le, W. Gong, N. M. Dunlop, J. L. Gao, P. M. Murphy, and J. M. Wang. 2001. Synthetic peptide MMK-1 is a highly specific chemotactic agonist for leukocyte FPRL1. J. Leukoc. Biol. 70: 155-161. (Pubitemid 32613676)
12. Christophe, T., A. Karlsson, C. Dugave, M. J. Rabiet, F. Boulay, and C. Dahlgren. 2001. The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. J. Biol. Chem. 276: 21585-21593.
13. Karlsson, J., A. L. Stenfeldt, M. J. Rabiet, J. Bylund, H. F. Forsman, and C. Dahlgren. 2009. The FPR2-specific ligand MMK-1 activates the neutrophil NADPH-oxidase, but triggers no unique pathway for opening of plasma membrane calcium channels. Cell Calcium 45: 431-438.
14. Le, Y., W. Gong, H. L. Tiffany, A. Tumanov, S. Nedospasov, W. Shen, N. M. Dunlop, J. L. Gao, P. M. Murphy, J. J. Oppenheim, and J. M. Wang. 2001. Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1. J. Neurosci. 21: RC123.
15. Fiore, S., S.W. Ryeom, P. F. Weller, and C. N. Serhan. 1992. Lipoxin recognition sites. Specific binding of labeled lipoxin A4 with human neutrophils. J. Biol. Chem. 267: 16168-16176.
16. Perretti, M., N. Chiang, M. La, I. M. Fierro, S. Marullo, S. J. Getting, E. Solito, and C. N. Serhan. 2002. Endogenous lipid- and peptide-derived antiinflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat. Med. 8: 1296-1302. (Pubitemid 35373563)
17. Ariel, A., N. Chiang, M. Arita, N. A. Petasis, and C. N. Serhan. 2003. Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-alpha secretion from human T cells. J. Immunol. 170: 6266-6272. (Pubitemid 36682612)
18. Maddox, J. F., M. Hachicha, T. Takano, N. A. Petasis, V. V. Fokin, and C. N. Serhan. 1997. Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor. J. Biol. Chem. 272: 6972-6978. (Pubitemid 27166397)
19. Gewirtz, A. T., L. S. Collier-Hyams, A. N. Young, T. Kucharzik, W. J. Guilford, J. F. Parkinson, I. R. Williams, A. S. Neish, and J. L. Madara. 2002. Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis. J. Immunol. 168: 5260-5267. (Pubitemid 34495994)
20. Godson, C., S. Mitchell, K. Harvey, N. A. Petasis, N. Hogg, and H. R. Brady. 2000. Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J. Immunol. 164: 1663-1667. (Pubitemid 30108713)
21. Maderna, P., S. Yona, M. Perretti, and C. Godson. 2005. Modulation of phagocytosis of apoptotic neutrophils by supernatant from dexamethasone-treated macrophages and annexin-derived peptide Ac(2-26). J. Immunol. 174: 3727-3733. (Pubitemid 40354084)
22. Heasman, S. J., K. M. Giles, C. Ward, A. G. Rossi, C. Haslett, and I. Dransfield. 2003. Glucocorticoid-mediated regulation of granulocyte apoptosis and macrophage phagocytosis of apoptotic cells: implications for the resolution of inflammation. J. Endocrinol. 178: 29-36. (Pubitemid 36927006)
23. Perretti, M., and F. N. Gavins. 2003. Annexin 1: an endogenous antiinflammatory protein. News Physiol. Sci. 18: 60-64.
24. Gavins, F. N., A. M. Kamal, M. D'Amico, S. M. Oliani, and M. Perretti. 2005. Formyl-peptide receptor is not involved in the protection afforded by annexin 1 in murine acute myocardial infarct. FASEB J. 19: 100-102. (Pubitemid 40069931)
25. Hayhoe, R. P., A. M. Kamal, E. Solito, R. J. Flower, D. Cooper, and M. Perretti. 2006. Annexin 1 and its bioactive peptide inhibit neutrophil- endothelium interactions under flow: indication of distinct receptor involvement. Blood 107: 2123-2130. (Pubitemid 43289398)
26. Gastardelo, T. S., A. S. Damazo, J. Dalli, R. J. Flower, M. Perretti, and S. M. Oliani. 2009. Functional and ultrastructural analysis of annexin A1 and its receptor in extravasating neutrophils during acute inflammation. Am. J. Pathol. 174: 177-183.
27. Devchand, P. R., M. Arita, S. Hong, G. Bannenberg, R. L. Moussignac, K. Gronert, and C. N. Serhan. 2003. Human ALX receptor regulates neutrophil recruitment in transgenic mice: roles in inflammation and host defense. FASEB J. 17: 652-659. (Pubitemid 37221150)
28. Levy, B. D., G. T. De Sanctis, P. R. Devchand, E. Kim, K. Ackerman, B. A. Schmidt, W. Szczeklik, J. M. Drazen, and C. N. Serhan. 2002. Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat. Med. 8: 1018-1023. (Pubitemid 35033707)
29. Dufton, N., R. Hannon, V. Brancaleone, J. Dalli, H. B. Patel, M. Gray, F. D'Acquisto, J. C. Buckingham, M. Perretti, and R. J. Flower. 2010. Antiinflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J. Immunol. 184: 2611-2619.
30. Chen, K., Y. Le, Y. Liu, W. Gong, G. Ying, J. Huang, T. Yoshimura, L. Tessarollo, and J. M. Wang. 2010. A critical role for the g protein-coupled receptor mFPR2 in airway inflammation and immune responses. J. Immunol. 184: 3331-3335.
31. Dufton, N., R. Hannon, V. Brancaleone, J. Dalli, H. B. Patel, M. Gray, F. D'Acquisto, J. C. Buckingham, M. Perretti, and R. J. Flower. 2010. Antiinflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. [Published erratum appears in 2011 J. Immunol. 186: 2684-2685.] J. Immunol. 184: 2611-2619.
32. Yang, D., Q. Chen, Y. Le, J. M. Wang, and J. J. Oppenheim. 2001. Differential regulation of formyl peptide receptor-like 1 expression during the differentiation of monocytes to dendritic cells and macrophages. J. Immunol. 166: 4092-4098. (Pubitemid 32224940)
33. Murphy, P. M., T. Ozçelik, R. T. Kenney, H. L. Tiffany, D. McDermott, and U. Francke. 1992. A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. J. Biol. Chem. 267: 7637-7643.
34. Mocellin, S., M. Panelli, E. Wang, C. R. Rossi, P. Pilati, D. Nitti, M. Lise, and F. M. Marincola. 2004. IL-10 stimulatory effects on human NK cells explored by gene profile analysis. Genes Immun. 5: 621-630. (Pubitemid 40045300)
35. Devosse, T., A. Guillabert, N. D'Haene, A. Berton, P. De Nadai, S. Noel, M. Brait, J. D. Franssen, S. Sozzani, I. Salmon, and M. Parmentier. 2009. Formyl peptide receptor-like 2 is expressed and functional in plasmacytoid dendritic cells, tissue-specific macrophage subpopulations, and eosinophils. J. Immunol. 182: 4974-4984.
36. O'Hara, R., E. P. Murphy, A. S. Whitehead, O. FitzGerald, and B. Bresnihan. 2004. Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis. Arthritis Rheum. 50: 1788-1799. (Pubitemid 38725091)
37. Gronert, K., A. Gewirtz, J. L. Madara, and C. N. Serhan. 1998. Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release. J. Exp. Med. 187: 1285-1294. (Pubitemid 28189117)
38. Sato, Y., H. Kitasato, Y. Murakami, A. Hashimoto, H. Endo, H. Kondo, M. Inoue, and I. Hayashi. 2004. Down-regulation of lipoxin A4 receptor by thromboxane A2 signaling in RAW246.7 cells in vitro and bleomycin-induced lung fibrosis in vivo. Biomed. Pharmacother. 58: 381-387. (Pubitemid 38951073)
39. Hashimoto, A., Y. Murakami, H. Kitasato, I. Hayashi, and H. Endo. 2007. Glucocorticoids co-interact with lipoxin A4 via lipoxin A4 receptor (ALX) upregulation. Biomed. Pharmacother. 61: 81-85. (Pubitemid 46188606)
40. Sawmynaden, P., and M. Perretti. 2006. Glucocorticoid upregulation of the annexin-A1 receptor in leukocytes. Biochem. Biophys. Res. Commun. 349: 1351-1355. (Pubitemid 44430195)
41. Iribarren, P., K. Chen, W. Gong, E. H. Cho, S. Lockett, B. Uranchimeg, and J. M. Wang. 2007. Interleukin 10 and TNFalpha synergistically enhance the expression of the G protein-coupled formylpeptide receptor 2 in microglia. Neurobiol. Dis. 27: 90-98. (Pubitemid 46921477)
42. Iribarren, P., K. Chen, J. Hu, W. Gong, E. H. Cho, S. Lockett, B. Uranchimeg, and J. M. Wang. 2005. CpG-containing oligodeoxynucleotide promotes microglial cell uptake of amyloid beta 1-42 peptide by up-regulating the expression of the G-protein- coupled receptor mFPR2. FASEB J. 19: 2032-2034. (Pubitemid 41759755)
43. Chen, K., J. Huang, Y. Liu, W. Gong, Y. Cui, and J. M. Wang. 2009. Synergy of TRIF-dependent TLR3 and MyD88-dependent TLR7 in up-regulating expression of mouse FPR2, a promiscuous G-protein-coupled receptor, in microglial cells. J. Neuroimmunol. 213: 69-77.
44. Chen, K., P. Iribarren, J. Huang, L. Zhang, W. Gong, E. H. Cho, S. Lockett, N. M. Dunlop, and J. M. Wang. 2007. Induction of the formyl peptide receptor 2 in microglia by IFN-gamma and synergy with CD40 ligand. J. Immunol. 178: 1759-1766. (Pubitemid 46154647)
45. Chen, K., L. Zhang, J. Huang, W. Gong, N. M. Dunlop, and J. M. Wang. 2008. Cooperation between NOD2 and Toll-like receptor 2 ligands in the up-regulation of mouse mFPR2, a G-protein-coupled Abeta42 peptide receptor, in microglial cells. J. Leukoc. Biol. 83: 1467-1475. (Pubitemid 351960328)
46. Tsuchiya, S., Y. Kobayashi, Y. Goto, H. Okumura, S. Nakae, T. Konno, and K. Tada. 1982. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 42: 1530-1536. (Pubitemid 12148801)
47. Dong, Z. M., S. M. Chapman, A. A. Brown, P. S. Frenette, R. O. Hynes, and D. D. Wagner. 1998. The combined role of P- and E-selectins in atherosclerosis. J. Clin. Invest. 102: 145-152. (Pubitemid 28323841)
48. Schreiber, E., P. Matthias, M. M. Müller, and W. Schaffner. 1989. Rapid detection of octamer binding proteins with 'mini-extracts,' prepared from a small number of cells. Nucleic Acids Res. 17: 6419. (Pubitemid 19198635)
49. Eguchi, J., Q. W. Yan, D. E. Schones, M. Kamal, C. H. Hsu, M. Q. Zhang, G. E. Crawford, and E. D. Rosen. 2008. Interferon regulatory factors are transcriptional regulators of adipogenesis. Cell Metab. 7: 86-94.
50. Mantovani, A., A. Sica, S. Sozzani, P. Allavena, A. Vecchi, and M. Locati. 2004. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25: 677-686. (Pubitemid 39457982)
51. Uranishi, M., S. Iida, T. Sanda, T. Ishida, E. Tajima, M. Ito, H. Komatsu, H. Inagaki, and R. Ueda. 2005. Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-gamma (MIG) gene expression in B-cell malignancy. Leukemia 19: 1471-1478. (Pubitemid 41136344)
52. Marié, I., J. E. Durbin, and D. E. Levy. 1998. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J. 17: 6660-6669. (Pubitemid 28521799)
53. Tamura, T., H. Yanai, D. Savitsky, and T. Taniguchi. 2008. The IRF family transcription factors in immunity and oncogenesis. Annu. Rev. Immunol. 26: 535-584. (Pubitemid 351600385)
54. Nakshatri, H., P. Nakshatri, and R. A. Currie. 1995. Interaction of Oct-1 with TFIIB. Implications for a novel response elicited through the proximal octamer site of the lipoprotein lipase promoter. J. Biol. Chem. 270: 19613-19623.
55. Sandelin, A., P. Carninci, B. Lenhard, J. Ponjavic, Y. Hayashizaki, and D. A. Hume. 2007. Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nat. Rev. Genet. 8: 424-436. (Pubitemid 46789243)
56. Lehtonen, A., S. Matikainen, and I. Julkunen. 1997. Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages. J. Immunol. 159: 794-803. (Pubitemid 127484231)
57. Darnell, J. E., Jr., I. M. Kerr, and G. R. Stark. 1994. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264: 1415-1421.
58. Gobin, S. J., P. Biesta, and P. J. Van den Elsen. 2003. Regulation of human beta 2-microglobulin transactivation in hematopoietic cells. Blood 101: 3058-3064. (Pubitemid 36857996)
59. Huang, H. Y., C. H. Chien, K. H. Jen, and H. D. Huang. 2006. RegRNA: an integrated web server for identifying regulatory RNA motifs and elements. Nucleic Acids Res. 34(Web Server issue): W429-434.
60. Calvo, S. E., D. J. Pagliarini, and V. K. Mootha. 2009. Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proc. Natl. Acad. Sci. USA 106: 7507-7512.
61. Hellen, C. U., and P. Sarnow. 2001. Internal ribosome entry sites in eukaryotic mRNA molecules. Genes Dev. 15: 1593-1612. (Pubitemid 32702581)
62. Kaspar, R. L., T. Kakegawa, H. Cranston, D. R. Morris, and M. W. White. 1992. A regulatory cis element and a specific binding factor involved in the mitogenic control of murine ribosomal protein L32 translation. J. Biol. Chem. 267: 508-514.
63. Mazumder, B., X. Li, and S. Barik. 2010. Translation control: a multifaceted regulator of inflammatory response. J. Immunol. 184: 3311-3319.
64. Lee, I., S. S. Ajay, J. I. Yook, H. S. Kim, S. H. Hong, N. H. Kim, S. M. Dhanasekaran, A. M. Chinnaiyan, and B. D. Athey. 2009. New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sites. Genome Res. 19: 1175-1183.
65. Lee, H. Y., M. K. Kim, K. S. Park, E. H. Shin, S. H. Jo, S. D. Kim, E. J. Jo, Y. N. Lee, C. Lee, S. H. Baek, and Y. S. Bae. 2006. Serum amyloid A induces contrary immune responses via formyl peptide receptor-like 1 in human monocytes. Mol. Pharmacol. 70: 241-248.
66. Schwab, J. M., N. Chiang, M. Arita, and C. N. Serhan. 2007. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447: 869-874. (Pubitemid 46920139)
67. Machado, F. S., J. E. Johndrow, L. Esper, A. Dias, A. Bafica, C. N. Serhan, and J. Aliberti. 2006. Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat. Med. 12: 330-334. (Pubitemid 43355082)
68. Alexander, W. S., and D. J. Hilton. 2004. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu. Rev. Immunol. 22: 503-529. (Pubitemid 38680432)
69. Russell, R., I. Gori, C. Pellegrini, R. Kumar, C. Achtari, and G. O. Canny. 2011. Lipoxin A4 is a novel estrogen receptor modulator. FASEB J. 25: 4326-4337.
70. Ribas, V., B. G. Drew, J. A. Le, T. Soleymani, P. Daraei, D. Sitz, L. Mohammad, D. C. Henstridge, M. A. Febbraio, S. C. Hewitt, et al. 2011. Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development. Proc. Natl. Acad. Sci. USA 108: 16457-16462.
71. Krishnamoorthy, S., A. Recchiuti, N. Chiang, S. Yacoubian, C. H. Lee, R. Yang, N. A. Petasis, and C. N. Serhan. 2010. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc. Natl. Acad. Sci. USA 107: 1660-1665.
72. Li, Y., L. Cai, H. Wang, P. Wu, W. Gu, Y. Chen, H. Hao, K. Tang, P. Yi, M. Liu, et al. 2011. Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2. Oncogene 30: 3887-3899.