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Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;7(4):475–486. doi: 10.1111/j.1582-4934.2003.tb00251.x

New asthma drugs acting on gene expression

F‐D Popescu 1
PMCID: PMC6740119  PMID: 14754517

Abstract

New asthma drugs acting on transcription are transcription factor agonists (dissociated steroids, peroxisome proliferator‐activated receptor gamma agonists), transcription factor inhibitors (NF‐kB / AP‐1 inhibitors, STAT6 inhibitors), inhibitors of protein kinases acting on transcription factors (p38 MAP kinase inhibitors), and chromatin modifying agents. Pharmacological approach of translation in asthma includes therapeutic ribozymes and antisense oligonucleotides targeting receptors (adenosine A1 receptor, alpha chain of IL‐5 receptor, common beta chain of IL‐3/IL‐5/GM‐CSF receptor), cytokines (IL‐4, IL‐5, SCF), signal transduction molecules (Syk, Lyn), transcription factors (STAT‐6, GATA‐3). Some of these drugs acting on gene expression have the potential to improve therapeutic benefits compared with traditional drugs.

Keywords: gene expression, transcription, transcription factors, translation

References

  • 1. Popescu F.D., Cellular and molecular pharmacology of inhaled corticosteroids and beta2‐agonists. Ed Sitech, Craiova, 2000, pp. 13–74.
  • 2. Newton R., Molecular mechanisms of glucocorticoid actions: what is important?, Thorax, 55: 603–613, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Gjomarkaj M., Synergy between long‐acting beta2‐agonists and inhaled glucocorticosteroids, Clinical implications, Rev. Patol. Respir., 5: 156–158, 2002. [Google Scholar]
  • 4. Belvisi M.G., Wicks S.L., Battram C.H., Bottoms S.E.W., Redford J.E., Woodman P., et al, Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity, J Immunol, 166: 1975–1982, 2001. [DOI] [PubMed] [Google Scholar]
  • 5. Dinca M., Popescu F.D., Vieru M., PPAR, PPAR agonists and apoptosis, actualities, Br. Med. J. (ed Rom), 9: 409–411, 2002. [Google Scholar]
  • 6. Wang A.C., Dai X., Luu B., Conrad D.J., Peroxisome proliferator‐activated receptor‐gamma regulates airway epithelial cell activation. Am. J. Respir. Cell. Mol. Biol., 24: 688, 2001. [DOI] [PubMed] [Google Scholar]
  • 7. Patel H.J., Belvisi M.G., Bishop‐Bailey D., Yacoub M.H., Mitchell J.A., Activation of peroxisome proliferator‐activated receptors in human airway smooth muscle cells has a superior anti‐inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy, J. Immunol., 170: 2663–2669, 2003. [DOI] [PubMed] [Google Scholar]
  • 8. Ward J.E., Gould H., Harris T., Stewart A., Novel antiproliferative mechanisms for PPAR gamma ligands, 15‐deoxy‐delta12,14‐prostaglandin J2 and rosiglitazone in human cultured airway smooth muscle, TSANZ Annual Scientific Meeting, Adelaide, April, P74, 2003.
  • 9. Ghosh S., Karin M., Missing pieces in the NF‐kB puzzle. Cell, 109: S81–S96, 2002. [DOI] [PubMed] [Google Scholar]
  • 10. Huang T.J., Adcock I.M., Chung K.F., A novel transcription factor, SP100030, inhibits cytokine gene expression, but not airway eosinophilia or hyperresponsiveness in sensitized and allergen‐exposed rat, Br. J. Pharmacol., 134: 1029–1036, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Henderson W.R., Chi E.C., Teo J.L., Nguyen C., Kahn M., A small molecule inhibitor of redox‐regulated NF‐kappaB and Activator Protein‐1 transcription blocks allergic airway inflammation in a mouse asthma model, J. Immunol., 169: 5294–5299. [DOI] [PubMed] [Google Scholar]
  • 12. Pelaia G., Vatrella A., Calabrese C., Mazzarella G., Marsico S.A., New perspectives in asthma treatment, Allergy, 55(suppl 61): 60, 2000. [DOI] [PubMed] [Google Scholar]
  • 13. Fujihara S., Ward C., Dransfield I., Hay R.T., Uings I.J., Hayes B., et al. Inhibition of nuclear factor‐kappaB activation un‐masks the ability of TNF‐alpha to induce human eosinophil apoptosis, Eur. J. Immunol., 32: 457–466, 2002. [DOI] [PubMed] [Google Scholar]
  • 14. Stolzenberger S., Haake A., Duschl A., Inhibition of STAT6 by an intracellularly delivered peptide, Immunobiol., 204: 29–30, 2001. [DOI] [PubMed] [Google Scholar]
  • 15. Underwood D.C., Griswold D.E. Inhibition of p38 MAP Kinase, In: Hansel T.T., Barnes P.J., eds., New drugs for asthma, allergy and COPD, Prog Respir Res, Basel , Karger, 2001, vol. 31, pp. 342–345. [Google Scholar]
  • 16. Vanden Berghe W., De Bosscher K., Vermeulen L., De Wilde G., Haegeman G., Induction and repression of NF‐kappa B‐driven inflammatory genes, Ernst Schering Res. Found Workshop, 40: 233–278, 2002. [DOI] [PubMed] [Google Scholar]
  • 17. Cui C.H., Adachi T., Oyamada H., Kamada Y., Kuwasaki T., Yamada Y. et al., The role of mitogen‐activated protein kinases in eotaxin‐induced cytokine production from bronchial epithelial cells, Am. J. Respir. Cell Mol. Biol., 27: 329–335, 2002. [DOI] [PubMed] [Google Scholar]
  • 18. Irusen E., Matthews J.G., Takahashi A., Barnes P.J., Chung K.F., Adcock I.M., p38 mitogen‐activated protein kinase‐induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid‐insensitive asthma, J. Allergy Clin. Immunol., 109: 649–657, 2002. [DOI] [PubMed] [Google Scholar]
  • 19. Urnov F.D., Wolffe A.P., Chromatin modification, In: Hansel T.T., Barnes P.J., eds., New drugs for asthma, allergy and COPD, Prog Respir Res, Basel , Karger, 2001, vol. 31, pp. 332–336. [Google Scholar]
  • 20. Sandberg J.A., Lee P.A., Usman L.N., Ribozyme therapy, In: Hansel T.T., Barnes P.J., eds., New drugs for asthma, allergy and COPD, Prog Respir Res Basel , Karger, 2001, vol. 31, pp. 370–373. [Google Scholar]
  • 21. Tanaka M., Nyce J., Respirable antisense oligonucleotides: a new drug class for respiratory disease, Respir. Res., 2: 5–9, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Nyce J., Respirable antisense oligonucleotides: a new, third drug class targeting respiratory disease, Curr. Opin. Allergy Clin. Immunol., 2: 533–536, 2002. [DOI] [PubMed] [Google Scholar]
  • 23. Lach‐Trifilieff E., McKay R.A., Monia B.P., Karras J.G., Walker C., In vitro and in vivo inhibition of interleukin (IL)‐5‐mediated eosinopoiesis by murine IL‐5Ralpha antisense oligonucleotides, Am. J. Respir. Cell. Mol. Biol., 24: 116–122, 2001. [DOI] [PubMed] [Google Scholar]
  • 24. Molet S., Ramos‐Barbon D., Martin J.G., Hamid Q., Adoptively transferred late allergic response is inhibited by IL‐4, but not IL‐5, antisense oligonucleotide. J. Allergy Clin. Immunol., 104: 1188, 1999. [DOI] [PubMed] [Google Scholar]
  • 25. Allakhverdi Z., Allam M., Renzi P.M. Inhibition of antigen‐induced eosinophilia and airway hyperresponsiveness by antisense oligonucleotides directed against the common beta chain of IL‐3, IL‐5, GM‐CSF receptors in a rat model of allergic asthma, Am. J. Respir. Crit. Care. Med., 165: 1015–1021, 2002. [DOI] [PubMed] [Google Scholar]
  • 26. Finotto S., Buerke M., Lingnau K., Schmitt E., Galle P.R., Neurath M.F. Local administration of antisense phosphorothioate oligonucleotides to the c‐kit ligand, stem cell factor, suppresses airway inflammation and IL‐4 production in a murine model of asthma, J. Allergy Clin. Immunol., 107: 279–286, 2001. [DOI] [PubMed] [Google Scholar]
  • 27. Stenton G.R., Ulanova M., Dery R.E., Merani S., Kim M.K., Gilchrist M., et al, Inhibition of allergic inflammation in the airways using aerosolized antisense to syk kinase, J. Immunol., 169: 1028–1036, 2002. [DOI] [PubMed] [Google Scholar]
  • 28. Stafford S., Lowell C., Sur S., Alam R., Lyn tyrosine kinase is important for IL‐5‐stimulated eosinophil differentiation, J. Immunol., 168: 1978–1983, 2002. [DOI] [PubMed] [Google Scholar]
  • 29. Bennett C.F. Antisense therapy In: Hansel T.T., Barnes P.J., eds., New drugs for asthma, allergy and COPD, Prog Respir Res, Basel , Karger, 2001, vol. 31, pp. 365–369. [Google Scholar]
  • 30. Finotto S., De Sanctis G. T., Lehr H.A., Herz U., Buerke M., Schipp M., et al, Treatment of allergic inflammation and hyperresponsiveness by antisense‐induced local blockade of GATA‐3 expression, J. Exp. Med., 193: 1247–1260, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Popescu F.D., New asthma drugs acting on gene expression, Annual Meeting of the Swiss Society for Allergology and Immunology and Swiss Society of Pneumology, St. Gallen, 2003, Main Lecture, Symposia Allergology and Pneumology: “United Airways”, Wissenschaftliches program, pp. 19.

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