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

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 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 1/2 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 kinasedependent 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. (J

Immune Activation in Functional Dyspepsia: Bystander Becoming the Suspect

“…Non-classical eosinophil inducers include epithelial-derived cytokines thymic stromal lymphopoietin (TSLP), IL-25 and IL-33, which activate eosinophils as part of a Type 2 allergic response, often in a cooperative manner and involving ILC2 induction ( Kim et al, 2013 ; Salimi et al, 2013 ; Han et al, 2017 , 2018 ). A novel epithelial regulator of eosinophil recruitment was recently discovered in a mouse model of allergic rhinitis where protein arginine methyltransferase 1 (PRMT1) promoted the production of TSLP, IL-25 and IL-33 ( Park et al, 2021 ). However, we found no difference in gene-expression of aforementioned cytokines in FD patients compared to healthy controls, suggesting that this pathway is not an essential contributor to eosinophilic infiltration in FD ( Ceulemans et al, 2021 ).…”

A Herbal Concoction of Cinnamomum cassia and Artemisa annua Extracts Ameliorates Allergic Rhinitis in OVA-Induced Balb/C Mice by Inhibiting Th2 Signaling

“…They further demonstrated that the elevated secretion of epithelial cytokines, including IL-25, IL-33, and TSLP, is essential for Th-2 cell differentiation. Thus, previous studies have established an association between the epithelium mediators IL-25, IL-33, and TSL, as well as IgE and IL-4 Th-2 signaling molecules with allergic rhinitis [8].…”

The potential roles of interleukin-25 in infectious diseases

“…It is well known that house dust mite (HDMs) is a major factor for allergic diseases, such as atopic dermatitis, allergic rhinitis, and asthma (67). HDM-specific immunoglobulins in serum are positively correlated with IL-25 expression, and IL-25 involved in the development of atopic dermatitis, allergic rhinitis, and asthma sensitized to HDM (68). For atopic dermatitis, intelectin (ITLN) is a key factor for the expression of IL-25 in airway epithelial cells and aggravates allergic airway inflammation (69).…”