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PRMT1 Upregulated by Epithelial Proinflammatory Cytokines Participates in COX2 Expression in Fibroblasts and Chronic Antigen-Induced Pulmonary Inflammation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Jul 01; Vol. 195 (1), pp. 298-306. Date of Electronic Publication: 2015 May 29. - Publication Year :
- 2015
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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.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Acute Disease
Animals
Antibodies pharmacology
Asthma chemically induced
Asthma genetics
Asthma pathology
Cell Proliferation
Chronic Disease
Culture Media, Conditioned pharmacology
Cyclooxygenase 2 genetics
Enzyme Inhibitors pharmacology
Epithelial Cells drug effects
Epithelial Cells pathology
Fibroblasts drug effects
Fibroblasts pathology
Gene Expression Regulation
Humans
Interleukin-4 pharmacology
Lung drug effects
Lung immunology
Lung pathology
Naphthalenesulfonates pharmacology
Ovalbumin
Pneumonia
Protein-Arginine N-Methyltransferases antagonists & inhibitors
Protein-Arginine N-Methyltransferases genetics
Rats
Signal Transduction
Transforming Growth Factor beta antagonists & inhibitors
Transforming Growth Factor beta genetics
Urea analogs & derivatives
Urea pharmacology
Vascular Endothelial Growth Factor A antagonists & inhibitors
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor A immunology
Asthma immunology
Cyclooxygenase 2 immunology
Epithelial Cells immunology
Fibroblasts immunology
Protein-Arginine N-Methyltransferases immunology
Transforming Growth Factor beta immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26026059
- Full Text :
- https://doi.org/10.4049/jimmunol.1402465