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.
journal_name
Int Forum Allergy Rhinoljournal_title
International forum of allergy & rhinologyauthors
Cho JS,Kim JA,Park JH,Park IH,Han IH,Lee HMdoi
10.1002/alr.21792subject
Has Abstractpub_date
2016-10-01 00:00:00pages
1020-1028issue
10eissn
2042-6976issn
2042-6984journal_volume
6pub_type
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