Increased SERPINB2 potentiates 15LO1 expression via STAT6 signalling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps

Chunyu Luo; Ying Zhu; Shiyao Zhang; Jiayao Zhou; Song Mao; Ru Tang; Yuelong Gu; Shaolin Tan; Hai Lin; Zhipeng Li; Weitian Zhang

doi:10.1111/cea.14484

Increased SERPINB2 potentiates 15LO1 expression via STAT6 signalling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps

Clin Exp Allergy. 2024 Apr 19. doi: 10.1111/cea.14484. Online ahead of print.

Authors

Chunyu Luo^{1

2

3}, Ying Zhu^{1

2

3}, Shiyao Zhang^{1

2

3}, Jiayao Zhou^{1

2

3}, Song Mao^{1

2

3}, Ru Tang^{1

2

3}, Yuelong Gu^{1

2

3}, Shaolin Tan^{1

2

3

4}, Hai Lin^{1

2

3}, Zhipeng Li^{1

2

3}, Weitian Zhang^{1

2

3}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, China.
³ Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, China.
⁴ Postgraduate Training Base of Shanghai Sixth People's Hospital, Jinzhou Medical University, Shanghai, China.

PMID: 38639267
DOI: 10.1111/cea.14484

Abstract

Background: SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling.

Methods: SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA.

Results: SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs in vitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1.

Conclusions: SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.

Keywords: 15‐lipoxygenase 1; SERPINB2; STAT6; chronic rhinosinusitis; epithelial cell; nasal polyps.

Abstract

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