Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Macrophage-Specific Transcription Factor Can Be Modified Posttranslationally by Ubiquitination in the Lipopolysaccharide-Treated Macrophages

  • Jung, Jae-Woo (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Choi, Jae-Chol (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Kim, Jae-Yeol (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Park, In-Won (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Choi, Byoung-Whui (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Shin, Jong-Wook (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Christman, John William (Department of Pulmonary, Critical Care and Sleep Medicine, University of Illinois College of Medicine)
  • Received : 2011.01.17
  • Accepted : 2011.01.19
  • Published : 2011.02.28
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Abstract

Background: Macrophages are one of the most important inflammatory cells in innate immunity. PU.1 is a macrophage-specific transcription factor. Ubiquitins are the ultimate regulator of eukaryotic transcription. The ubiquitination process for PU.1 is unknown. This study investigated the lipopolysaccharide (LPS)-induced activation of PU.1 and its relation to ubiquitins in the macrophages. Methods: Raw264.7 cells, the primary cultured alveolar, pulmonary, and bone marrow derived macrophages were used. The Raw264.7 cells were treated with MG-132, $NH_4Cl$, lactacytin and LPS. Nitric oxide and prostaglandin D2 and E2 were measured. Immunoprecipitation and Western blots were used to check ubiquitination of PU.1. Results: The PU.1 ubiquitination increased after LPS ($1{\mu}g$/mL) treatment for 4 hours on Raw264.7 cells. The ubiquitination of PU.1 by LPS was increased by MG-132 or $NH_4Cl$ pretreatment. Two hours of LPS treatment on macrophages, PU.1 activation was not induced nor increased with the inhibition of proteasomes and/or lysosomes. The ubiquitination of PU.1 was increased in LPS-treated Raw264.7 cells at 12- and at 24 hours. LPS-treated cells increased nitric oxide production, which was diminished by MG-132 or $NH_4Cl$. LPS increased the production of $PGE_2$ in the alveolar and peritoneal macrophages of wild type mice; however, $PGE_2$ was blocked or diminished in Rac2 null mice. Pretreatment of lactacystin increased $PGE_2$, however it decreased the $PGD_2$ level in the macrophages derived from the bone marrow of B57/BL6 mice. Conclusion: LPS treatment in the macrophages ubiquitinates PU.1. Ubiquitination of PU.1 may be involved in synthesis of nitric oxide and prostaglandins.

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References

  1. Chopra M, Reuben JS, Sharma AC. Acute lung injury: apoptosis and signaling mechanisms. Exp Biol Med (Maywood) 2009;234:361-71. https://doi.org/10.3181/0811-MR-318
  2. Bellingan GJ. The pulmonary physician in critical care 6: the pathogenesis of ALI/ARDS. Thorax 2002;57: 540-6. https://doi.org/10.1136/thorax.57.6.540
  3. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008;8: 958-69. https://doi.org/10.1038/nri2448
  4. Joo M, Kwon M, Azim AC, Sadikot RT, Blackwell TS, Christman JW. Genetic determination of the role of PU.1 in macrophage gene expression. Biochem Biophys Res Commun 2008;372:97-102. https://doi.org/10.1016/j.bbrc.2008.04.189
  5. Joo M, Kwon M, Cho YJ, Hu N, Pedchenko TV, Sadikot RT, et al. Lipopolysaccharide-dependent interaction between PU.1 and c-Jun determines production of lipocalin- type prostaglandin D synthase and prostaglandin D2 in macrophages. Am J Physiol Lung Cell Mol Physiol 2009;296:L771-9. https://doi.org/10.1152/ajplung.90320.2008
  6. Shibata Y, Berclaz PY, Chroneos ZC, Yoshida M, Whitsett JA, Trapnell BC. GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1. Immunity 2001;15:557-67. https://doi.org/10.1016/S1074-7613(01)00218-7
  7. Mazzi P, Donini M, Margotto D, Wientjes F, Dusi S. IFN-gamma induces gp91phox expression in human monocytes via protein kinase C-dependent phosphorylation of PU.1. J Immunol 2004;172:4941-7. https://doi.org/10.4049/jimmunol.172.8.4941
  8. Lowenstein CJ, Alley EW, Raval P, Snowman AM, Snyder SH, Russell SW, et al. Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci USA 1993;90:9730-4. https://doi.org/10.1073/pnas.90.20.9730
  9. Hochstrasser M. Origin and function of ubiquitin-like proteins. Nature 2009;458:422-9. https://doi.org/10.1038/nature07958
  10. Sun F, Anantharam V, Zhang D, Latchoumycandane C, Kanthasamy A, Kanthasamy AG. Proteasome inhibitor MG-132 induces dopaminergic degeneration in cell culture and animal models. Neurotoxicology 2006;27:807-15. https://doi.org/10.1016/j.neuro.2006.06.006
  11. Barringhaus KG, Matsumura ME. The proteasome inhibitor lactacystin attenuates growth and migration of vascular smooth muscle cells and limits the response to arterial injury. Exp Clin Cardiol 2007;12:119-24.
  12. Hart PD, Young MR. Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast. J Exp Med 1991;174:881-9. https://doi.org/10.1084/jem.174.4.881
  13. Cao H, Xiao L, Park G, Wang X, Azim AC, Christman JW, et al. An improved LC-MS/MS method for the quantification of prostaglandins $E_2$ and $D_2$ production in biological fluids. Anal Biochem 2008;372:41-51. https://doi.org/10.1016/j.ab.2007.08.041
  14. Zhang DE, Hetherington CJ, Chen HM, Tenen DG. The macrophage transcription factor PU.1 directs tissue- specific expression of the macrophage colony-stimulating factor receptor. Mol Cell Biol 1994;14:373-81. https://doi.org/10.1128/MCB.14.1.373
  15. Tazawa R, Hamano E, Arai T, Ohta H, Ishimoto O, Uchida K, et al. Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2005;171: 1142-9. https://doi.org/10.1164/rccm.200406-716OC
  16. Rothenberg EV, Scripture-Adams DD. Competition and collaboration: GATA-3, PU.1, and Notch signaling in early T-cell fate determination. Semin Immunol 2008; 20:236-46. https://doi.org/10.1016/j.smim.2008.07.006
  17. Feldman AL, Arber DA, Pittaluga S, Martinez A, Burke JS, Raffeld M, et al. Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Blood 2008;111:5433-9. https://doi.org/10.1182/blood-2007-11-124792
  18. Marques C, Pereira P, Taylor A, Liang JN, Reddy VN, Szweda LI, et al. Ubiquitin-dependent lysosomal degradation of the HNE-modified proteins in lens epithelial cells. FASEB J 2004;18:1424-6.
  19. Alonso S, Pethe K, Russell DG, Purdy GE. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc Natl Acad Sci USA 2007;104:6031-6. https://doi.org/10.1073/pnas.0700036104
  20. Hirose S, Nishizumi H, Sakano H. Pub, a novel PU.1 binding protein, regulates the transcriptional activity of PU.1. Biochem Biophys Res Commun 2003;311:351-60. https://doi.org/10.1016/j.bbrc.2003.09.212
  21. Bohuslav J, Chen LF, Kwon H, Mu Y, Greene WC. p53 induces NF-kappaB activation by an IkappaB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1. J Biol Chem 2004; 279:26115-25. https://doi.org/10.1074/jbc.M313509200
  22. Reyes-Turcu FE, Ventii KH, Wilkinson KD. Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 2009;78:363-97. https://doi.org/10.1146/annurev.biochem.78.082307.091526
  23. Joo HY, Zhai L, Yang C, Nie S, Erdjument-Bromage H, Tempst P, et al. Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature 2007;449:1068-72. https://doi.org/10.1038/nature06256
  24. Gammoh N, Gardiol D, Massimi P, Banks L. The Mdm2 ubiquitin ligase enhances transcriptional activity of human papillomavirus E2. J Virol 2009;83:1538-43. https://doi.org/10.1128/JVI.01551-08
  25. Bachmaier K, Toya S, Gao X, Triantafillou T, Garrean S, Park GY, et al. E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Nat Med 2007;13:920-6. https://doi.org/10.1038/nm1607
  26. Yedgar S, Krimsky M, Cohen Y, Flower RJ. Treatment of inflammatory diseases by selective eicosanoid inhibition: a double-edged sword? Trends Pharmacol Sci 2007;28:459-64. https://doi.org/10.1016/j.tips.2007.07.005
  27. Medeiros AI, Serezani CH, Lee SP, Peters-Golden M. Efferocytosis impairs pulmonary macrophage and lung antibacterial function via PGE2/EP2 signaling. J Exp Med 2009;206:61-8. https://doi.org/10.1084/jem.20082058
  28. Song L, Bhattacharya S, Yunus AA, Lima CD, Schindler C. Stat1 and SUMO modification. Blood 2006;108: 3237-44. https://doi.org/10.1182/blood-2006-04-020271
  29. Tillmanns S, Otto C, Jaffray E, Du Roure C, Bakri Y, Vanhille L, et al. SUMO modification regulates MafBdriven macrophage differentiation by enabling Myb-dependent transcriptional repression. Mol Cell Biol 2007; 27:5554-64. https://doi.org/10.1128/MCB.01811-06

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