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Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines

 Ji-Yeon Park  ;  Joo-Hee Choi  ;  Sang-Nam Lee  ;  Hyung-Ju Cho  ;  Ji-Suk Ahn  ;  Yong-Bum Kim  ;  Do-Yong Park  ;  Sang Chul Park  ;  Soo-In Kim  ;  Min-Jung Kang  ;  Ah-Ra Jang  ;  Jae-Hun Ahn  ;  Tae-Sung Lee  ;  Dong-Yeon Kim  ;  Sung Jae Shin  ;  Joo-Heon Yoon  ;  Jong-Hwan Park 
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol.147(5) : 1720-1731, 2021-05 
Journal Title
Issue Date
MAPKs ; PRMT1 ; allergic rhinitis (AR) ; epithelial cytokines ; house dust mite (HDM)
Background: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. Objective: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). Methods: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. Results: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. Conclusions: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Yoon, Joo Heon(윤주헌)
Lee, Sang Nam(이상남)
Cho, Hyung Ju(조형주) ORCID logo https://orcid.org/0000-0002-2851-3225
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