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