Display options
Share it on

Allergy Asthma Immunol Res. 2014 Sep;6(5):449-57. doi: 10.4168/aair.2014.6.5.449. Epub 2014 Jun 04.

Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-κB Pathways in Nasal Polyp-Derived Fibroblasts.

Allergy, asthma & immunology research

Jung-Sun Cho, In-Hye Han, Hye Rim Lee, Heung-Man Lee

Affiliations

  1. Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea. ; Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul, Korea.
  2. Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
  3. Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea. ; Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul, Korea. ; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.

PMID: 25229003 PMCID: PMC4161687 DOI: 10.4168/aair.2014.6.5.449

Abstract

PURPOSE: Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect.

METHODS: Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-κB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-κB was evaluated by western blot analysis.

RESULTS: PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-κB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8.

CONCLUSIONS: PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-κB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.

Keywords: Akt; E prostanoid receptor; Nasal polyps; interleukin-6; interleukin-8; prostaglandins E

References

  1. Otolaryngol Head Neck Surg. 1998 Apr;118(4):504-11 - PubMed
  2. Arthritis Res. 2000;2(5):356-60 - PubMed
  3. Mediators Inflamm. 2012;2012:645383 - PubMed
  4. Annu Rev Pharmacol Toxicol. 2001;41:661-90 - PubMed
  5. Thorax. 2006 Feb;61(2):129-33 - PubMed
  6. Mayo Clin Proc. 2011 May;86(5):427-43 - PubMed
  7. Curr Opin Allergy Clin Immunol. 2003 Feb;3(1):1-6 - PubMed
  8. J Int Med Res. 2006 Sep-Oct;34(5):520-4 - PubMed
  9. J Neurochem. 2001 Dec;79(5):950-8 - PubMed
  10. Pulm Pharmacol Ther. 2012 Feb;25(1):115-8 - PubMed
  11. Clin Exp Allergy. 2012 Jun;42(6):872-82 - PubMed
  12. J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):395-400 - PubMed
  13. Front Neurol. 2012 Oct 22;3:145 - PubMed
  14. Eur Arch Otorhinolaryngol. 2006 Mar;263(3):282-9 - PubMed
  15. Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):413-21 - PubMed
  16. Allergy. 2007 Apr;62(4):348-58 - PubMed
  17. Am J Otolaryngol. 1995 Mar-Apr;16(2):98-102 - PubMed
  18. Clin Immunol. 2006 Jun;119(3):229-40 - PubMed
  19. Am J Physiol. 1998 Oct;275(4):C988-94 - PubMed
  20. Am J Physiol Lung Cell Mol Physiol. 2012 Jan 15;302(2):L266-73 - PubMed
  21. Mol Cancer. 2010 Apr 30;9:97 - PubMed
  22. Int J Biochem Cell Biol. 2004 Jul;36(7):1187-205 - PubMed
  23. J Allergy Clin Immunol. 2009 Apr;123(4):868-74.e13 - PubMed
  24. Respirology. 2013 May;18(4):711-7 - PubMed
  25. Am J Rhinol Allergy. 2011 Jan-Feb;25(1):15-8 - PubMed
  26. Am J Physiol Cell Physiol. 2010 Jun;298(6):C1445-56 - PubMed
  27. Otolaryngol Head Neck Surg. 1997 Nov;117(5):535-41 - PubMed
  28. J Nutr. 2004 Aug;134(8 Suppl):2117S-2119S - PubMed
  29. Invest Ophthalmol Vis Sci. 2011 Jul 01;52(7):4859-65 - PubMed
  30. Br J Pharmacol. 2009 Feb;156(3):475-85 - PubMed

Publication Types