Rhinitis, sinusitis, and ocular allergy
Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines

https://doi.org/10.1016/j.jaci.2020.12.646Get rights and content
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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.

Key words

PRMT1
allergic rhinitis (AR)
epithelial cytokines
MAPKs
house dust mite (HDM)

Abbreviations used

ADMA
Asymmetric dimethylarginine
AIPI
Antigen-induced pulmonary inflammation
AMI-1
Arginine N-methyltransferase inhibitor-1
AR
Allergic rhinitis
COPD
Chronic obstructive pulmonary disease
COX2
Cyclooxygenase-2
HDM
House dust mite
MAPK
Mitogen-activated protein kinase
NAL
Nasal lavage
NF-κB
Nuclear factor kappa B
PRMT
Protein arginine methyltransferase
PRMT1+/−
PRMT1-haploinsufficient
TSLP
Thymic stromal lymphopoietin
WT
Wild-type

Cited by (0)

∗Sang Chul Park, MD, PhD, is currently at the Department of Otorhinolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.

This research was supported by the Global Research Lab Program (grant no. 2016K1A1A2910779) and the Mid-Career Researcher Program (grant no. 2018R1A2B3004143) of the National Research Foundation of Korea funded by the Ministry of Science and Information and Communication Technologies.

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.