RORα overexpression reduced interleukin-33 expression and prevented mast cell degranulation and inflammation by inducing autophagy in allergic rhinitis

Wangbo Yu; Jingwei Du; Lijuan Peng; Tao Zhang

doi:10.1002/iid3.1017

RORα overexpression reduced interleukin-33 expression and prevented mast cell degranulation and inflammation by inducing autophagy in allergic rhinitis

Immun Inflamm Dis. 2023 Oct;11(10):e1017. doi: 10.1002/iid3.1017.

Authors

Wangbo Yu^{1

2}, Jingwei Du³, Lijuan Peng⁴, Tao Zhang¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
² Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
³ Department of Otolaryngology-Head and Neck Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China.
⁴ Department of Microbiology and Immunology, School of Basic Medical Sciences，North Sichuan Medical College, Nanchong, Sichuan, China.

Abstract

Background: Retinoid acid receptor related orphan receptor α (RORα) is a nuclear receptor that along with other bioactive factors regulates cell proliferation, differentiation, and immunomodulation in vivo.

Aims: The objective of this study was to explore the function and mechanism of RORα in allergic rhinitis (AR).

Materials and methods: Derp1 was used to construct an AR cell model in HNEpC cells, and RORα was overexpressed or silenced in the AR HNEpC cells. Next, LAD2 cells were co-cultured with the Derp1-treated HNEpC cells. Additionally, an AR mouse model was established using by OVA, and a RORα Adenovirus was delivered by nebulizing. Pathological tissue structures were evaluated by hematoxylin-eosin staining, and the levels of RORα, interleukin-33 (IL-33), and other proteins were analyzed immunohistochemistry, western blotting, and immunofluorescence staining. IL-33, IL-4, IL-5, and IL-13 levels were detected using enzyme-linked immunosorbent assay kits and cell migration was assessed by Transwell assays.

Results: Our data showed that RORα was downregulated in the nasal mucosa tissues of AR patients. Derp1 treatment could cause a downregulation of RORα, upregulation of IL-33, the induction of NLRP3 inflammasomes, and cell migration in HNEpC cells. Furthermore, RORα overexpression dramatically attenuated IL-33 levels, NLRP3 inflammasome activity, and the migration of AR HNEpC cells induced with Derp1. Moreover, RORα in AR HNEpC cells could prevent mast cell (MC) degranulation and inflammation by accelerating autophagy, RORα overexpression inhibited MC degranulation and NLRP3-induced inflammation in the AR model mice. RORα overexpression reduced IL-33 expression in nasal epithelial cells, and also suppressed MC degranulation and inflammation by promoting autophagy.

Conclusion: RORα inhibits NLRP3 inflammasome in HNEpC, and attenuated mast cells degranulation and inflammation through autophagy in AR.

Keywords: allergic rhinitis; autophagy; interleukin-33; mast cell degranulation; retinoid acid receptor related orphan receptor α.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy
Cell Degranulation
Humans
Inflammasomes / metabolism
Inflammation
Interleukin-33
Mast Cells* / pathology
Mice
NLR Family, Pyrin Domain-Containing 3 Protein
Rhinitis, Allergic* / pathology

Substances

Inflammasomes
Interleukin-33
NLR Family, Pyrin Domain-Containing 3 Protein
Rora protein, mouse
Il33 protein, mouse