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Stellari FF, Sala A, Donofrio G, et al. Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study. Pharmacol Res Perspect. 2014;2(5):e00058doi: 10.1002/prp2.58.
Stellari, F. F., Sala, A., Donofrio, G., Ruscitti, F., Caruso, P., Topini, T. M., Francis, K. P., Li, X., Carnini, C., Civelli, M., & Villetti, G. (2014). Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study. Pharmacology research & perspectives, 2(5), e00058. https://doi.org/10.1002/prp2.58
Stellari, Fabio F, et al. "Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study." Pharmacology research & perspectives vol. 2,5 (2014): e00058. doi: https://doi.org/10.1002/prp2.58
Stellari FF, Sala A, Donofrio G, Ruscitti F, Caruso P, Topini TM, Francis KP, Li X, Carnini C, Civelli M, Villetti G. Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study. Pharmacol Res Perspect. 2014 Oct;2(5):e00058. doi: 10.1002/prp2.58. Epub 2014 Jul 02. PMID: 25505605; PMCID: PMC4186419.
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Pharmacol Res Perspect. 2014 Oct;2(5):e00058. doi: 10.1002/prp2.58. Epub 2014 Jul 02.

Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study.

Pharmacology research & perspectives

Fabio F Stellari, Angelo Sala, Gaetano Donofrio, Francesca Ruscitti, Paola Caruso, Thomas M Topini, Kevin P Francis, Xiaojian Li, Chiara Carnini, Maurizio Civelli, Gino Villetti

Affiliations

  1. Chiesi Farmaceutici S.p.A Parma, Italy.
  2. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano Milano, Italy ; Consiglio Nazionale delle Ricerche, IBIM Palermo, Italy.
  3. Dipartimento di Scienze Medico-Veterinarie, Università di Parma Parma, Italy.
  4. Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Università di Parma Parma, Italy.
  5. Perkin Elmer Discovery Services Hanover, Maryland.
  6. Perkin Elmer Alameda, California.

PMID: 25505605 PMCID: PMC4186419 DOI: 10.1002/prp2.58

Abstract

We studied in vivo the potential involvement of nuclear factor-κB (NF-κB) pathway in the molecular mechanism of the anti-inflammatory and immunomodulatory activity of azithromycin in the lung. Mice transiently transfected with the luciferase gene under the control of a NF-κB responsive element were used to assess in vivo NF-κB activation by bioluminescence imaging. Bioluminescence as well as inflammatory cells and concentrations of proinflammatory cytokines in bronchoalveolar lavage fluids, were monitored in an acute model of pulmonary inflammation resulting from intratracheal instillation of lipopolysaccharide. Lipopolysaccharide (LPS) instillation induced a marked increase in lung bioluminescence in mice transiently transfected with the luciferase gene under the control of an NF-κB responsive element, with significant luciferase expression in resident cells such as endothelial and epithelial cells, as assessed by duoplex immunofluorescence staining. Activation of NF-κB and inflammatory cell lung infiltration linearly correlated when different doses of bortezomib were used to inhibit NF-κB activation. Pretreatment with azithromycin significantly decreased lung bioluminescence and airways cell infiltration induced by LPS, also reducing proinflammatory cytokines concentrations in bronchoalveolar lavages and inhibiting NF-κB nuclear translocation. The results obtained using a novel approach to monitor NF-κB activation, provided, for the first time, in vivo evidence that azithromycin treatment results in pulmonary anti-inflammatory activity associated with the inhibition of NF-κB activation in the lung.

Keywords: Acute lung inflammation; azithromycin; bioluminescence; in vivo imaging; nuclear factor-κB

References

  1. Trends Cell Biol. 2012 Nov;22(11):557-66 - PubMed
  2. PLoS One. 2011;6(9):e25093 - PubMed
  3. Cell Microbiol. 2004 Apr;6(4):303-17 - PubMed
  4. J Inflamm (Lond). 2010 Apr 26;7:20 - PubMed
  5. Cell. 1986 Dec 26;47(6):921-8 - PubMed
  6. Int J Biol Sci. 2009 Oct 23;5(7):667-78 - PubMed
  7. J Immunol. 1999 Dec 15;163(12):6827-33 - PubMed
  8. Clin Exp Immunol. 2011 Dec;166(3):385-92 - PubMed
  9. Nat Med. 2001 Dec;7(12 ):1291-7 - PubMed
  10. Int J Chron Obstruct Pulmon Dis. 2008;3(3):331-50 - PubMed
  11. Vet Pathol. 2001 May;38(3):297-310 - PubMed
  12. Eur Respir J. 2012 Aug;40(2):485-94 - PubMed
  13. Am J Physiol Cell Physiol. 2003 Oct;285(4):C813-22 - PubMed
  14. Clin Microbiol Rev. 2010 Jul;23(3):590-615 - PubMed
  15. Br J Pharmacol. 2012 Mar;165(5):1348-60 - PubMed
  16. Br J Pharmacol. 2010 Aug;160(7):1573-6 - PubMed
  17. Am J Respir Cell Mol Biol. 1994 Oct;11(4):464-72 - PubMed
  18. Ageing Res Rev. 2008 Apr;7(2):83-105 - PubMed
  19. Antimicrob Agents Chemother. 2004 May;48(5):1581-5 - PubMed
  20. Exp Lung Res. 2009 Aug;35(6):439-85 - PubMed
  21. J Heart Lung Transplant. 2008 Nov;27(11):1210-6 - PubMed
  22. J Pharmacol Exp Ther. 2000 Jan;292(1):156-63 - PubMed
  23. Am J Physiol. 1999 Apr;276(4 Pt 1):C856-64 - PubMed
  24. Immunity. 1995 May;2(5):493-506 - PubMed
  25. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1095-101 - PubMed
  26. Basic Res Cardiol. 2001 Feb;96(1):50-8 - PubMed
  27. N Engl J Med. 2011 Aug 25;365(8):689-98 - PubMed
  28. Eur J Pharmacol. 2001 Oct 19;429(1-3):209-29 - PubMed
  29. J Immunol. 2001 Aug 1;167(3):1592-600 - PubMed
  30. Eur J Nucl Med Mol Imaging. 2013 Oct;40(10):1607-17 - PubMed
  31. Lancet. 2012 Aug 18;380(9842):660-7 - PubMed
  32. Am J Respir Cell Mol Biol. 2004 Apr;30(4):569-75 - PubMed
  33. Am J Physiol Lung Cell Mol Physiol. 2003 Apr;284(4):L566-77 - PubMed
  34. Brain Res. 2004 May 22;1008(2):284-7 - PubMed
  35. J Periodontol. 2011 Nov;82(11):1623-31 - PubMed
  36. Biochem Pharmacol. 2000 Oct 15;60(8):1085-9 - PubMed
  37. J Pharmacol Exp Ther. 2009 Oct;331(1):104-13 - PubMed
  38. Mol Cancer. 2010 Mar 10;9:56 - PubMed
  39. J Immunol. 2002 Feb 1;168(3):1441-6 - PubMed
  40. Pediatr Res. 2007 Oct;62(4):483-8 - PubMed
  41. J Immunol. 2006 Apr 15;176(8):4995-5005 - PubMed
  42. Chest. 2001 Apr;119(4):1294-5 - PubMed
  43. Antimicrob Agents Chemother. 2007 Mar;51(3):975-81 - PubMed
  44. Eur J Immunol. 1999 Jun;29(6):1890-900 - PubMed
  45. PLoS One. 2012;7(8):e42454 - PubMed
  46. Int Immunopharmacol. 2011 Apr;11(4):424-34 - PubMed

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