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
- Authors
- Cho, Jung-Sun; Kim, Jin-Ah; Park, Joo-Hoo; Park, Il-Ho; Han, In-Hye; Lee, Heung-Man
- Issue Date
- 10월-2016
- Publisher
- WILEY-BLACKWELL
- Keywords
- chronic rhinosinusitis; nasal polyp; Toll-like receptor; interleukin-32; fibroblast; ex vivo explant
- Citation
- INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY, v.6, no.10, pp.1020 - 1028
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
- Volume
- 6
- Number
- 10
- Start Page
- 1020
- End Page
- 1028
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/87344
- DOI
- 10.1002/alr.21792
- ISSN
- 2042-6976
- 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 polypderived 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 ofmitogen-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 in-duction 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. (C) 2016 ARS-AAOA, LLC.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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