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J. Allergy Clin. Immunol., Available online 18 January 2021 | https://doi.org/10.1016/j.jaci.2020.12.646 Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines

Ji-Yeon Park BS^a, Joo-Hee Choi PhD^a, Sang-Nam Lee PhD^b, Hyung-Ju Cho MD, PhD^c, Ji-Suk Ahn BS^b, Yong-Bum Kim PhD^d, Do-Yong Park MS^d, Sang-Chul Park MD, PhD^c, Soo-In Kim MS^e, Min-Jung Kang PhD^a, Ah-Ra Jang BS^a, Jae-Hun Ahn DVM^a, Tae-Sung Lee DVM^a, Dong-Yeon Kim DVM^a, Sung Jae Shin DVM, PhD^f, Joo-Heon Yoon MD, PhD^b,c,*, Jong-Hwan Park DVM, PhD^a,*

^aLaboratory Animal Medicine, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju, Republic of Korea
^bThe Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
^cDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea
^dCenter for Nonclinical Studies, Korea Institute of Toxicology, Daejeon, Republic of Korea
^eThe Research Center for Human Natural Defense System, Yonsei University College of Medicine, Korea
^fDepartment of Microbiology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea

^*Corresponding author

Abstract

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 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 (AMI-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 (WT) 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 (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 (MAPK)-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. AMI-1 treatment alleviated AR in the mouse model.

Conclusion
PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

논문정보

형식Research article
게재일2021년 01월 (BRIC 등록일 2021-01-28)
연구진국내 연구진
분야 의약학 > 면역의학

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