title: PRMT1 Upregulated by Epithelial Proinflammatory Cytokines Participates in COX2 Expression in Fibroblasts and Chronic Antigen-Induced Pulmonary Inflammation.
abstract: Protein arginine methyltransferase (PRMT)1, methylating both histones and key cellular proteins, has emerged as a key regulator of various cellular processes. This study aimed to identify the mechanism that regulates PRMT1 in chronic Ag-induced pulmonary inflammation (AIPI) in the E3 rat asthma model. E3 rats were challenged with OVA for 1 or 8 wk to induce acute or chronic AIPI. Expression of mRNAs was detected by real-time quantitative PCR. PRMT1, TGF-β, COX2, and vascular endothelial growth factor protein expression in lung tissues was determined by immunohistochemistry staining and Western blotting. In the in vitro study, IL-4-stimulated lung epithelial cell (A549) medium (ISEM) with or without anti-TGF-β Ab was applied to human fibroblasts from lung (HFL1). The proliferation of HFL1 was determined by MTT. AMI-1 (pan-PRMT inhibitor) was administered intranasally to chronic AIPI rats to determine PRMT effects on asthmatic parameters. In lung tissue sections, PRMT1 expression was significantly upregulated, mainly in epithelial cells, in acute AIPI lungs, whereas it was significantly upregulated mainly in fibroblasts in chronic AIPI lungs. The in vitro study revealed that ISEM elevates PRMT1, COX2, and vascular endothelial growth factor expressions, and it promoted fibroblast proliferation. The application of anti-TGF-β Ab suppressed COX2 upregulation by ISEM. AMI-1 inhibited the expression of COX2 in TGF-β-stimulated cells. In the in vivo experiment, AMI-1 administered to AIPI rats reduced COX2 production and humoral immune response, and it abrogated mucus secretion and collagen generation. These findings suggested that TGF-β-induced PRMT1 expression participates in fibroblast proliferation and chronic airway inflammation in AIPI.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China; University Hospital Basel, University of Basel, 4031 Basel, Switzerland; and.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: University Hospital Basel, University of Basel, 4031 Basel, Switzerland; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Jia
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Qirui
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Ruanjuan
authors.initials: R
authors.lastname: Bao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Congshan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China;
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China; shemin.lu@gmail.com ewsr1@163.com.
authors.forename: Xudong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, People's Republic of China; Department of Epidemiology and Health Statistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China shemin.lu@gmail.com ewsr1@163.com.
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
mesh_terms: D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002908:Chronic Disease; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009282:Naphthalenesulfonates / Q000494:pharmacology; D010047:Ovalbumin; D011014:Pneumonia; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D051381:Rats; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: C535077:7,7'-carbonylbis(azanediyl) bis(4-hydroxynaphthalene-2-sulfonic acid; D000906:Antibodies; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D009282:Naphthalenesulfonates; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D015847:Interleukin-4; D014508:Urea; D010047:Ovalbumin; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C546338:Prmt1 protein, mouse; D011484:Protein-Arginine N-Methyltransferases