title: Upregulated protein arginine methyltransferase 1 by IL-4 increases eotaxin-1 expression in airway epithelial cells and participates in antigen-induced pulmonary inflammation in rats.
abstract: Protein arginine methyltransferases (PRMTs), catalyzing methylation of both histones and other cellular proteins, have emerged as key regulators of various cellular processes. This study aimed to identify key PRMTs involved in Ag-induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of PRMT1 in the IL-4-induced eosinophil infiltration process. E3 rats were i.p. sensitized with OVA/alum and intranasally challenged with OVA to induce AIPI. The expressions of PRMT1-6, eotaxin-1, and CCR3 in lungs were screened by real-time quantitative PCR. Arginine methyltransferase inhibitor 1 (AMI-1, a pan-PRMT inhibitor) and small interfering RNA-PRMT1 were used to interrupt the function of PRMT1 in A549 cells. In addition, AMI-1 was administrated intranasally to AIPI rats to observe the effects on inflammatory parameters. The results showed that PRMT1 expression was mainly expressed in bronchus and alveolus epithelium and significantly upregulated in lungs from AIPI rats. The inhibition of PRMTs by AMI-1 and the knockdown of PRMT1 expression were able to downregulate the expressions of eotaxin-1 and CCR3 with the IL-4 stimulation in the epithelial cells. Furthermore, AMI-1 administration to AIPI rats can also ameliorate pulmonary inflammation, reduce IL-4 production and humoral immune response, and abrogate eosinophil infiltration into the lungs. In summary, PRMT1 expression is upregulated in AIPI rat lungs and can be stimulated by IL-4. Intervention of PRMT1 activity can abrogate IL-4-dependent eotaxin-1 production to influence the pulmonary inflammation with eosinophil infiltration. The findings may provide experimental evidence that PRMT1 plays an important role in asthma pathogenesis.
authors.affiliation: Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Sun
authors.forename: Xudong
authors.initials: X
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.forename: Fangfang
authors.initials: F
authors.lastname: Jiao
authors.forename: Chenyan
authors.initials: C
authors.lastname: Li
authors.forename: Dongmin
authors.initials: D
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D000941:Antigens / Q000633:toxicity*; D001249:Asthma / Q000378:metabolism; D054413:Chemokine CCL11 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D009282:Naphthalenesulfonates / Q000494:pharmacology / Q000627:therapeutic use; D010047:Ovalbumin / Q000633:toxicity; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012137:Respiratory System / Q000166:cytology; D013047:Specific Pathogen-Free Organisms; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C535077:7,7'-carbonylbis(azanediyl) bis(4-hydroxynaphthalene-2-sulfonic acid; D000941:Antigens; D054413:Chemokine CCL11; C508598:IL4 protein, human; D009282:Naphthalenesulfonates; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D015847:Interleukin-4; D014508:Urea; D010047:Ovalbumin; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases