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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:147

Article

Park, Ji-Yeon^1,2  Choi, Joo-Hee^1,2  Lee, Sang-Nam³  Cho, Hyung-Ju⁴  Ahn, Ji-Suk³  Kim, Yong-Bum⁵  Park, Do-Yong⁵  Park, Sang Chul^4,8  Kim, Soo-In⁶  Kang, Min-Jung^1,2  Jang, Ah-Ra^1,2  Ahn, Jae-Hun^1,2  Lee, Tae-Sung^1,2  Kim, Dong-Yeon^1,2  Shin, Sung Jae⁷  Yoon, Joo-Heon^3,4  Park, Jong-Hwan^1,2 

[1] Chonnam Natl Univ, Coll Vet Med, Lab Anim Med, 77 Yongbong Ro, Gwangju 61186, South Korea

[2] Chonnam Natl Univ, Anim Med Inst, Gwangju, South Korea

[3] Yonsei Univ, Airway Mucus Inst, Coll Med, Seoul, South Korea

[4] Yonsei Univ, Dept Otorhinolaryngol, Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea

[5] Korea Inst Toxicol, Ctr Nonclin Studies, Daejeon, South Korea

[6] Yonsei Univ, Res Ctr Human Nat Ural Def Syst, Coll Med, Seoul, South Korea

[7] Yonsei Univ, Inst Immunol & Immunol Dis, Dept Microbiol, Coll Med, Seoul, South Korea

[8] Hallym Univ, Kangnam Sacred Heart Hosp, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Seoul, South Korea

关键词: PRMT1;    allergic rhinitis (AR);    epithelial cytokines;    MAPKs;    house dust mite (HDM);   

DOI  :  10.1016/j.jaci.2020.12.646

来源: Elsevier

【 摘 要 】

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 T(H)2 (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.

【 授权许可】

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