Skip to main content

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 507))

  • 431 Accesses

Abstract

A large body of experimental evidence has implicated the cysteinyl leukotrienes in a variety of inflammatory responses201C;2. Leukotriene C4 (LTC4) synthase (Mr of 16,568; EC#2.5.1.37) is a selective, membrane-bound glutathione-S-transferase that catalyzes the conversion of LTA4 to LTC4. Although LTC4 synthase enzymatic activity is found in various cell types, mRNA for LTC4 synthase is present only in eosinophils, basophils, mast cells, and cells of monocyte/macrophage lineage. Previous studies suggest that LTC4 synthase expression is increased in the bronchial mucosa of patients with aspirin-sensitive asthma3. The gene for LTC4 synthase has been cloned, sequenced, and mapped to the distal region of chromosome 545. The LTC4 synthase 5’ flanking region lacks a TATA box but has known consensus sites for ets, AP-1, AP-2, and Sp145. Previous work from our laboratory indicates that LTC4 synthase gene expression is upregulated by transforming growth factor-ß (TGF-ß) through a transcriptional mechanism in the monocyte-like cell line, THP-16. The purpose of this study was to begin to investigate the molecular mechanisms of regulation of transcription of the LTC4 synthase gene in mononuclear phagocytes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lewis, R.A., K.F. Austen, and R.J. Soberman, Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases, N. Engl. J. Med. 323: 645–655 (1990).

    Article  CAS  PubMed  Google Scholar 

  2. Namovic, M.T., R.E. Walsh, C. Goodfellow, R.R. Harris, G.W. Carter, and R.L. Bell, Pharmacological modulation of eosinophil influx into the lungs of Brown Norway rats, Eur. J. of Pharmacol. 315: 81–88 (1996).

    Article  CAS  Google Scholar 

  3. Cowburn, A.S., K. Sladek, J. Soja, L. Adamek, E. Nizankowska, A. Szczeklik, B.K. Lam, J.F. Penrose, K.F. Austen, S.T. Holgate, and A.P. Sampson, Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma, J. Clin. Invest. 101: 834–846 (1997).

    Article  Google Scholar 

  4. Bigby, T.D., C.R. Hodulik, K.C. Arden, and L. Fu., Molecular cloning of the human leukotriene C4 synthase gene and assignment to chromosome 5q35, Mol. Med. 2: 637–646 (1996).

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Penrose, J.F., J. Spector, M. Baldasaro, K. Xu, J. Boyce, J.P. Arm, K.F. Austen, and B.K. Lam, Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5g35, J. Biol. Chem. 271: 11356–11361 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Riddick, C.A., K.J. Serio, C.R. Hodulik, W.L. Ring, M.S. Regan, and T.D. Bigby, TGF-13 increases leukotriene C4 synthase expression in the monocyte-like cell line, THP-1, J. Immunol. 162: 1102–1107 (1999).

    Google Scholar 

  7. Hagen, G., S. Muller, M. Beato, and G. Suske, Cloning by recognition site screening of two novel GT box binding proteins: a family of Spl related genes, Nucl. Acids Res. 20: 5519–5525 (1992).

    Article  CAS  Google Scholar 

  8. Kingsley, C. and A. Winoto, Cloning of GT binding proteins: a novel Spl multigene family regulating T-cell receptor gene expression, Mol. Cell Biol. 12: 4251–4261 (1992).

    CAS  Google Scholar 

  9. Kadonaga, J.T., K.R. Carter, F.R. Marsiarz, and R. Tjian, Isolation of cDNA encoding transcription factor Spl and functional analysis of the DNA binding domain, Cell 51: 1079–1090 (1987).

    Article  CAS  PubMed  Google Scholar 

  10. Hoey, T., R.O.J. Weinzierl, G. Gill, J.-L. Chen, B.D. Dynlacht, and R. Tjian, Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators, Cell 72: 247–260 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Majello, B., P. De Luca, and L. Lania, Sp3 is a bifunctional regulator with modular independent activation and repression domains, J. Biol. Chem. 272: 4021–4026 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Hauses, M., R.R. Tonjes, and M. Grez, The transcription factor Sp1 regulates the myeloid-specific expression of the human hematopoietic cell kinase (HCK) gene through binding to two adjacent GC boxes within the HCK promoter-proximal region, J. Biol. Chem. 273: 31844–31852 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Shou, Y., S. Baron, and M. Ponce, An Spl -binding silencer element is a critical negative regulator of the megakaryocyte-specific a1Ib gene, J. Biol. Chem. 273: 5716–5726 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Black, A.R., D. Jensen, S. Lin, and J.C. Azizkhan, Growth/cell cycle regulation of Spl phosphorylation, J. Biol. Chem 274: 1207–1215 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Han, I. and J.E. Kudlow, Reduced O glycosylation of Spl is associated with increased proteasome susceptibility, Mol. Cell. Biol. 17: 2550–2558 (1997).

    CAS  Google Scholar 

  16. Zhang, D.E., C.J. Hetherington, S. Tan, S.E. Dziennis, D.A. Gonzalez, H.M. Chen, and D.G. Tenen, Sp1 is a critical factor for the monocytic specific expression of human CD14, J. Biol. Chem. 269: 11425–11434 (1994).

    CAS  PubMed  Google Scholar 

  17. Ebert, S.N. and D.L. Wong, Differential Activation of the Rat Phenylethanolamine N-Methyltransferase Gene by Spl and Egr-1, J. Biol. Chem. 270: 17299–17305 (1995).

    Article  CAS  PubMed  Google Scholar 

  18. Hagen, G., J. Dennig, A. Preiss, M. Beato, and G. Suske, Functional analyses of the transcription factor Sp4 properties distinct from Spl and Sp3, J. Biol. Chem. 270: 24989–24994 (1995).

    Article  CAS  PubMed  Google Scholar 

  19. Li, R., Z. Hodny, K. Luciakova, P. Barath, and B.D. Nelson, Spl Activates and Inhibits Transcription from Separate Elements in the Proximal Promoter of the Human Adenine Nucleotide Translocase 2 (ANT2) Gene, J. Biol. Chem. 271: 18925–18930 (1996).

    Article  CAS  PubMed  Google Scholar 

  20. Majello, B., P. De Luca, G. Hagen, G. Suske, and L. Lania, Different members of the Spl multigene family exert opposite transcriptional regulation of the long-terminal repeat of HIV-1, Nucl. Acids Res. 22: 4914–4921 (1994).

    Article  CAS  Google Scholar 

  21. Rajakumar, R. A., S. Thamotharan, R.K. Menon, and S.U. Devaskar, Spl and Sp3 regulate transcriptional activity of the facilitative glucose transporter isoform-3 gene in mammalian neuroblast and trophoblasts, J. Biol Chem 273(42), 27474–27483 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Bigger, C.B., I.N. Melnikova, and P.D. Gardner, Spl and Sp3 regulate expression of the neuronal nicotinic acetycholine receptor 134 subunit gene, J. Biol. Chem. 272: 25976–25982 (1997).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Serio, K.J., Hodulik, C.R., Bigby, T.D. (2002). Regulation Of Leukotriene C4 Synthase Gene Expression By Sp1 And Sp3 In Mononuclear Phagocytes. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E., Serhan, C. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5. Advances in Experimental Medicine and Biology, vol 507. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0193-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0193-0_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4960-0

  • Online ISBN: 978-1-4615-0193-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics