Korean J Otorhinolaryngol-Head Neck Surg.  2020 May;63(5):206-215. 10.3342/kjorl-hns.2019.00738.

Nucleotide-Binding Oligomerization Domain-Like Receptor 3 Inflammasome Inhibition by MCC950 Reduces the Lipopolysaccharide-Induced Interleukin-1β in Cultured Dispersed Nasal Polyp Cells

Affiliations
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon, Korea
  • 2Department of Otorhinolaryngology-Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun, China
  • 3State Key Laboratory of Respiratory Disease, Department of Otorhinolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
  • 4Department of Ophthalmology, Chungnam National University School of Medicine, Daejeon, Korea
  • 5Department of Human Environment and Design, Yonsei University College of Social Science, Seoul, Korea

Abstract

Background and Objectives
The nucleotide-binding oligomerization domain-like receptor (NLRP) 3 is known as a member of the NLR family, and it has been confirmed that the NLRP3 inflammasome is associated with various diseases such as asthma, inflammatory bowel disease, metabolic disorders and multiple sclerosis, as well as other auto-immune and auto-inflammatory diseases. However, the role of NLRP3 in chronic rhinosinusitis with nasal polyps (CRSwNP) has not yet been explored. Subjects and Method Forty-four specimens of nasal polyps and 25 specimens of uncinate processes were collected from patients with chronic rhinosinusitis with nasal polyps, and 25 specimens of uncinate tissues were collected from patients who underwent other rhino-surgeries. The western blot assay was employed to analyze the expression of NLRP3; interleukin (IL)-1β and IL-17A were detected using immunohistochemistry and real-time polymerase chain reaction. The production of lipopolysaccharide (LPS) induced IL-1β and IL-17A with or without the NLRP3 inflammasome inhibitor (MCC950) was measured using an enzyme linked immunosorbent assay in cultured dispersed nasal polyp cells.
Results
NLRP3 showed a high level of expression in nasal polyps than in the control group (p<0.01). The expression of IL-1β and IL-17A was significantly higher in nasal polyps in the CRSwNP group than in the control group (p<0.05). LPS-induced production of IL-1β was significantly suppressed by treatment with the NLRP3 inflammasome inhibitor (p<0.05).
Conclusion
The NLRP3 inflammasome plays an essential role in the pathogenesis of CRSwNP, and thus MCC950 can be considered a prospective therapeutic for NLRP3 inflammasome-mediated inflammation in nasal polyps. Our data provide new evidence that IL-17A is involved in inflammasome-associated inflammation in nasal polyps.

Keyword

Inflammasome; Interleukins; Nasal polyps; Sinusitis
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