Nuclear receptor 4a3 (Nr4a3) regulates murine mast cell responses and granule content

PLoS ONE

Volumn 9, Issue 2, 2014, Pages

  Garcia Faroldi, Gianni ^a   Melo, Fabio R ^a   Bruemmer, Dennis ^b   Conneely, Orla M ^c   Pejler, Gunnar ^a   Lundequist, Anders ^a  

^a SWEDISH UNIVERSITY OF AGRICULTURAL SCIENCES   (Sweden)

^b UNIVERSITY OF KENTUCKY   (United States)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN E RECEPTOR; INTERLEUKIN 13; INTERLEUKIN 6; MAST CELL PROTEASE 6; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; NUCLEAR RECEPTOR 4A3; TRANSCRIPTION FACTOR; TRYPTASE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CHEMOKINE; CYTOKINE; DNA BINDING PROTEIN; IMMUNOGLOBULIN E; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NERVE PROTEIN; NR4A3 PROTEIN, MOUSE; STEROID RECEPTOR; THYROID HORMONE RECEPTOR;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CELL ACTIVATION; CELL FUNCTION; CELL GRANULE; CONTROLLED STUDY; CYTOKINE RELEASE; ENZYME ACTIVITY; IMMUNOREGULATION; MAST CELL; MOUSE; NONHUMAN; NR4A3 GENE; SECRETORY GRANULE; TPSB2 GENE; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; ANIMAL; APOPTOSIS; BONE MARROW CELL; C57BL MOUSE; CELL CULTURE; CELL PROLIFERATION; CYTOLOGY; DRUG EFFECTS; GENETICS; IMMUNOLOGY; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; BLOTTING, WESTERN; BONE MARROW CELLS; CELL PROLIFERATION; CELLS, CULTURED; CHEMOKINES; CYTOKINES; CYTOPLASMIC GRANULES; DNA-BINDING PROTEINS; IMMUNOGLOBULIN E; MAST CELLS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NERVE TISSUE PROTEINS; NF-KAPPA B; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTORS, IGE; RECEPTORS, STEROID; RECEPTORS, THYROID HORMONE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SIGNAL TRANSDUCTION; TRYPTASES;

EID: 84895862885     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0089311     Document Type: Article

References (47)

1. Galli SJ, Grimbaldeston M, Tsai M (2008) Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol 8: 478-486. (Pubitemid 351733419)
2. Metcalfe DD, Baram D, Mekori YA (1997) Mast cells. Physiol Rev 77: 1033-1079. (Pubitemid 27459579)
3. Lundequist A, Pejler G Biological implications of preformed mast cell mediators. Cell Mol Life Sci 68: 965-975.
4. Pejler G, Rönnberg E, Waern I, Wernersson S (2010) Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 115: 4981-4990.
5. Murakami M, Iwata Y, Funaba M (2007) Expression and transcriptional activity of alternative splice variants of Mitf exon 6. Mol Cell Biochem 303: 251-257. (Pubitemid 47261324)
6. Arinobu Y, Iwasaki H, Akashi K (2009) Origin of basophils and mast cells. Allergol Int 58: 21-28.gov/pubmed/19153533. Accessed 2012 Dec 10.
7. Kitamura Y (2003) Heterogeneity of Mast Cells and Phenotypic Change Between Subpopulations. Annu Rev Immunol 7: 59-76. Available: http://dx.doi.org/10.1146/annurev.iy.07.040189.000423.
8. Galli SJ, Borregaard N, Wynn TA (2011) Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol 12: 1035-1044.
9. Beaudry G, Langlois MC, Weppe I, Rouillard C, Lévesque D (2000) Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain. J Neurochem 75: 1694-1702.
10. Glass CK, Saijo K (2010) Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol 10: 365-376.
11. Maheux J, Ethier I, Rouillard C, Lévesque D (2005) Induction patterns of transcription factors of the nur family (nurr1, nur77, and nor-1) by typical and atypical antipsychotics in the mouse brain: implication for their mechanism of action. J Pharmacol Exp Ther 313: 460-473. (Pubitemid 40411373)
12. Maxwell MA, Muscat GEO (2006) The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. Nucl Recept Signal 4: e002.
13. Pols TWH, Bonta PI, de Vries CJM (2007) NR4A nuclear orphan receptors: protective in vascular disease? Curr Opin Lipidol 18: 515-520. (Pubitemid 47462203)
14. Thompson J, Burger ML, Whang H, Winoto A (2010) Protein kinase C regulates mitochondrial targeting of Nur77 and its family member Nor-1 in thymocytes undergoing apoptosis. Eur J Immunol 40: 2041-2049.
15. Cheng LE, Chan FK, Cado D, Winoto A (1997) Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J 16: 1865-1875. (Pubitemid 27170948)
16. Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM, et al. (2011) The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes. Nat Immunol 12: 778-785.
17. Bonta PI, van Tiel CM, Vos M, Pols TWH, van Thienen J V, et al. (2006) Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses. Arterioscler Thromb Vasc Biol 26: 2288-2294. (Pubitemid 44465724)
18. Pei L, Castrillo A, Tontonoz P (2006) Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77. Mol Endocrinol 20: 786-794. Available: http://www.ncbi.nlm.nih.gov/pubmed/16339277. Accessed 2012 Nov 12.
19. Rönnberg E, Guss B, Pejler G (2010) Infection of mast cells with live streptococci causes a toll-like receptor 2- and cell-cell contact-dependent cytokine and chemokine response. Infect Immun 78: 854-864.
20. Lundequist A, Calounova G, Wensman H, Rönnberg E, Pejler G (2011) Differential regulation of Nr4a subfamily nuclear receptors following mast cell activation. Mol Immunol 48: 1753-1761.
21. Nomiyama T, Nakamachi T, Gizard F, Heywood EB, Jones KL, et al. (2006) The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation. J Biol Chem 281: 33467-33476. (Pubitemid 46036728)
22. Rönnberg E, Pejler G (2012) Serglycin: the master of the mast cell. Methods Mol Biol 836: 201-217.
23. Duelli A, Ronnberg E, Waern I, Ringvall M, Kolset SO, et al. (2009) Mast Cell Differentiation and Activation Is Closely Linked to Expression of Genes Coding for the Serglycin Proteoglycan Core Protein and a Distinct Set of Chondroitin Sulfate and Heparin Sulfotransferases. J Immunol 183: 7073-7083.
24. Peng Y, Power MR, Li B, Lin T-J (2005) Inhibition of IKK down-regulates antigen+IgE-induced TNF production by mast cells: a role for the IKK-IkappaB-NF-kappaB pathway in IgE-dependent mast cell activation. J Leukoc Biol 77: 975-983. (Pubitemid 40770850)
25. Nakagomi D, Suzuki K, Nakajima H (2012) Critical roles of IκB kinase subunits in mast cell degranulation. Int Arch Allergy Immunol 158 Suppl : 92-95. Available:
26. Klein M, Klein-Hessling S, Palmetshofer A, Serfling E, Tertilt C, et al. (2006) Specific and redundant roles for NFAT transcription factors in the expression of mast cell-derived cytokines. J Immunol 177: 6667-6674. (Pubitemid 44715030)
27. Hernandez-Hansen V, Smith AJ, Surviladze Z, Chigaev A, Mazel T, et al. (2004) Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. J Immunol 173: 100-112. (Pubitemid 38797331)
28. Parravicini V, Gadina M, Kovarova M, Odom S, Gonzalez-Espinosa C, et al. (2002) Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nat Immunol 3: 741-748.
29. Tshori S, Razin E (2010) Editorial: Mast cell degranulation and calcium entry-the Fyn-calcium store connection. J Leukoc Biol 88: 837-838.
30. Pullen NA, Falanga YT, Morales JK, Ryan JJ (2012) The Fyn-STAT5 Pathway: A New Frontier in IgE- and IgG-Mediated Mast Cell Signaling. Front Immunol 3: 117.
31. Martin SJ, Lennon S V, Bonham AM, Cotter TG (1990) Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis. J Immunol 145: 1859-1867. (Pubitemid 20336755)
32. Melo FR, Lundequist A, Calounova G, Wernersson S, Pejler G (2011) Lysosomal membrane permeabilization induces cell death in human mast cells. Scand J Immunol 74: 354-362.
33. Cerella C, Coppola S, Maresca V, De Nicola M, Radogna F, et al. (2009) Multiple mechanisms for hydrogen peroxide-induced apoptosis. Ann N Y Acad Sci 1171: 559-563.
34. Melo FR, Waern I, Rönnberg E, Åbrink M, Lee DM, et al. (2011) A role for serglycin proteoglycan in mast cell apoptosis induced by a secretory granule-mediated pathway. J Biol Chem 286: 5423-5433.
35. Kolset SO, Pejler G (2011) Serglycin: a structural and functional chameleon with wide impact on immune cells. J Immunol 187: 4927-4933.
36. Hallgren J, Pejler G (2006) Biology of mast cell tryptase. An inflammatory mediator. FEBS J 273: 1871-1895. Available:
37. Lundequist A, Pejler G (2011) Biological implications of preformed mast cell mediators. Cell Mol Life Sci 68: 965-975.
38. Morii E, Tsujimura T, Jippo T, Hashimoto K, Takebayashi K, et al. (1996) Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by the mi locus. Blood 88: 2488-2494. (Pubitemid 26327498)
39. Ogihara H, Kanno T, Morii E, Kim DK, Lee YM, et al. (1999) Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene. Oncogene 18: 4632-4639. (Pubitemid 29405895)
40. Kim D-K, Lee Y-M (2004) Requirement of c-jun transcription factor on the mouse mast cell protease-6 expression in the mast cells. Arch Biochem Biophys 431: 71-78. (Pubitemid 39349359)
41. Thakurdas SM, Melicoff E, Sansores-Garcia L, Moreira DC, Petrova Y, et al. (2007) The mast cell-restricted tryptase mMCP-6 has a critical immunoprotective role in bacterial infections. J Biol Chem 282: 20809-20815. (Pubitemid 47099914)
42. Hamilton MJ, Sinnamon MJ, Lyng GD, Glickman JN, Wang X, et al. (2011) Essential role for mast cell tryptase in acute experimental colitis. Proc Natl Acad Sci U S A 108: 290-295.
43. Shin K, Nigrovic PA, Crish J, Boilard E, McNeil HP, et al. (2009) Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes. J Immunol 182: 647-656.
44. Waern I, Karlsson I, Thorpe M, Schlenner SM, Feyerabend TB, et al. (2012) Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis. Biol Chem 393: 1555-1567.
45. Waern I, Lundequist A, Pejler G, Wernersson S (2012) Mast cell chymase modulates IL-33 levels and controls allergic sensitization in dust-mite induced airway inflammation. Mucosal Immunol.
46. Piliponsky AM, Chen C-C, Grimbaldeston MA, Burns-Guydish SM, Hardy J, et al. (2010) Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice. Am J Pathol 176: 926-938.
47. Zhao W, Oskeritzian CA, Pozez AL, Schwartz LB (2005) Cytokine production by skin-derived mast cells: endogenous proteases are responsible for degradation of cytokines. J Immunol 175: 2635-2642. (Pubitemid 41113878)