Effects of Pendrin Protein in Nasal Epithelial Cells on Mucin Production in the Context of Type 2 Inflammation

Nongping Zhong; Honghui Ai; Wei Zhong; Xiaoyan Huang; Kai Wang; Qing Luo; Jieqing Yu

doi:10.3390/jpm13030502

Effects of Pendrin Protein in Nasal Epithelial Cells on Mucin Production in the Context of Type 2 Inflammation

J Pers Med. 2023 Mar 10;13(3):502. doi: 10.3390/jpm13030502.

Authors

Nongping Zhong¹, Honghui Ai¹, Wei Zhong¹, Xiaoyan Huang¹, Kai Wang², Qing Luo¹, Jieqing Yu^{1

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Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
² Department of Otorhinolaryngology, The 908th Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Nanchang 330006, China.
³ Department of Allergy, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
⁴ Jiangxi Otorhinolaryngology Head and Neck Surgery Institute, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Abstract

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease. The pathogenesis of chronic sinusitis is still unclear; however, the nasal cavity and paranasal sinuses are commonly affected by type 2 inflammation, which is caused by Th2 cytokines such as interleukin (IL)-5, IL-4, and IL-13. Previous studies have shown that pendrin promotes local infiltration of neutrophils through the production of human neutrophil elastase (HNE), which is essential for the secretion of mucin 5AC (MUC5AC) in chronic inflammatory diseases of the lower respiratory tract. This study investigated pendrin expression and its relationship to mucin in type 2 inflammation.

Methods: A total of 40 patients (10 CRS patients with nasal polyps,10 CRS patients without nasal polyps, and 20 nasal septum deviation patients) were included in this study and were divided into the CRS group and the NC group. A normal nasal mucosa tissue culture model was established in vitro. IL-13 was used to stimulate primary cultures of human nasal epithelial cells (HNECs). Western blot (WB), enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of pendrin, MUC5AC, and MUC5B. After transfecting HNECs with siRNA pendrin or negative control (NC), EGF receptor (EGFR), HNE, MUC5AC, and MUC5B expression were analyzed using qRT-PCR, WB, or ELISA in terms of their relationships with pendrin. Pendrin expression in the tissue was also analyzed.

Results: After IL-13 stimulation, pendrin, MUC5AC, and MUC5B expression levels were upregulated; the optimal concentration of IL-13 was 50 ng/mL. The expression levels of HNE, EGFR, MUC5AC, and MUC5B were downregulated after transfection with siRNA pendrin-1650. Pendrin expression in the NC group was lower than in the CRS group.

Conclusion: IL-13 is implicated in the inflammation of nasal mucosa, and pendrin is closely related to the excessive secretion of mucin. The expression of mucin is downregulated after transfection with siRNA pendrin. There is a positive relationship between pendrin and EFGR/HNE. Moreover, pendrin plays an important role in type 2 inflammation.

Keywords: chronic rhinosinusitis; mucin; pendrin; type 2 inflammation.

Abstract

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