Toll-like receptor 4–mediated expression of interleukin-32 via the c-Jun N-terminal kinase/protein kinase B/cyclic adenosine monophosphate response element binding protein pathway in chronic rhinosinusitis with nasal polyps

Jung Sun Cho, Jin Ah Kim, Joo Hoo Park, Il Ho Park, In Hye Han, Heung Man Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is prolonged inflammation of the sinonasal mucosa. Interleukin-32 (IL-32) is involved in the pathogenesis of chronic lung inflammatory diseases. The aim of study is to compare the expression level of IL-32 in normal nasal mucosa and CRSwNP and to investigate the mechanism underlying IL-32 expression in CRSwNP. Methods: IL-32 expression in nasal tissues, normal nasal mucosa–derived fibroblasts (NorDFs) and nasal polyp–derived fibroblasts (NPDFs), ex vivo explants of nasal tissues was measured by reverse-transcription polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). NorDFs and NPDFs were exposed to lipopolysaccharide (LPS) and the expression level of IL-32 was measured. LPS from Rhodobactersphaeroides (RS) and small interference RNA against Toll-like receptor 4 (siTLR4) were used to inhibit signaling by TLR4. Activation of mitogen-activated protein kinase (MAPKs) (extracellular related kinase [ERK], p38, and c-Jun N-terminal kinase [JNK]), protein kinase B (AKT), and cyclic adenosine monophosphate response element binding protein (CREB) was examined using western blot analysis. Results: Expression of IL-32 was increased in CRSwNP compared to normal nasal mucosa. LPS induced expression of IL-32 in a time-dependent manner. The induction of IL-32 expression in NPDFS was more effective than in NorDFs. Treatment with RS and siTLR4 inhibited the messenger RNA (mRNA) expression of TLR4, myeloid differentiation primary response 88 (MyD88), and IL-32 in LPS-stimulated NPDFs. IL-32 expression was specifically activated by JNK, AKT, and CREB in LPS-stimulated NPDFs and CRSwNP ex vivo explants. Conclusion: The sensitivity for IL-32 expression by LPS was increased in CRSwNP compared to normal nasal mucosa. LPS effectively induced IL-32 expression in NPDFs than in NorDFs through the TLR4-JNK-AKT-CREB signaling pathway. Therefore, IL-32 seems to be involved in the pathogenesis of CRSwNP.

Original languageEnglish
Pages (from-to)1020-1028
Number of pages9
JournalInternational Forum of Allergy and Rhinology
Volume6
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

Keywords

  • chronic rhinosinusitis
  • ex vivo explant
  • fibroblast
  • interleukin-32
  • nasal polyp
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

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