Abstract
Protein arginine methyltransferase 1 (PRMT1) catalyzes methylation of histones and other cellular proteins, and thus regulates gene transcription and protein activity. In antigen-induced pulmonary inflammation (AIPI) PRMT1 was up-regulated in the epithelium, while in chronic AIPI, increased PRMT1 shifted to fibroblasts. In this study we investigated the cell type specific regulatory mechanism of PRMT1. Epithelial cells and fibroblasts were stimulated with IL-4 or IL-1β. Gene and protein expression were determined by RT-qPCR, immunohistochemistry staining and Western blotting. Signaling pathway inhibitors, siRNAs and shRNA were used to determine the regulatory mechanism of PRMT1. The results showed that IL-4 up-regulated PRMT1 through STAT6 signaling in epithelial cells, while IL-1β regulated PRMT1 through NF-κB in fibroblasts. The NF-kB inhibitor protein RKIP was highly expressed in epithelial cells and blocked IL-1β induced PRMT1 up-regulation; while the STAT6 inhibitor protein PIAS1 was expressed in fibroblasts and suppressed IL-4 induced PRMT1 expression. Furthermore, IL-4 stimulated epithelial cells to release IL-1β which up-regulated PRMT1 expression in fibroblasts. In conclusion, the inhibitor proteins RKIP and PIAS1 regulated the cell type and signaling specific expression of PRMT1. Thus PRMT1 expression in structural lung cells in asthma can be considered as potential target for new therapeutic intervention.
MeSH terms
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A549 Cells
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Binding Sites
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Blotting, Western
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Cells, Cultured
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Humans
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Immunoprecipitation
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Interleukin-1beta / pharmacology
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Interleukin-4 / genetics
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Interleukin-4 / metabolism
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Interleukin-4 / pharmacology
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Lung / metabolism
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Lung / pathology
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Microscopy, Fluorescence
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Phosphatidylethanolamine Binding Protein / antagonists & inhibitors
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Phosphatidylethanolamine Binding Protein / genetics
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Phosphatidylethanolamine Binding Protein / metabolism*
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Phosphorylation / drug effects
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Pneumonia / metabolism
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Pneumonia / pathology
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Promoter Regions, Genetic
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Protein Inhibitors of Activated STAT / antagonists & inhibitors
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Protein Inhibitors of Activated STAT / genetics
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Protein Inhibitors of Activated STAT / metabolism*
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Protein-Arginine N-Methyltransferases / antagonists & inhibitors
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Protein-Arginine N-Methyltransferases / genetics
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Protein-Arginine N-Methyltransferases / metabolism*
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Real-Time Polymerase Chain Reaction
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / pharmacology
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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STAT6 Transcription Factor / antagonists & inhibitors
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STAT6 Transcription Factor / genetics
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STAT6 Transcription Factor / metabolism
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Signal Transduction / drug effects
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Small Ubiquitin-Related Modifier Proteins / antagonists & inhibitors
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Small Ubiquitin-Related Modifier Proteins / genetics
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Small Ubiquitin-Related Modifier Proteins / metabolism*
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Up-Regulation / drug effects
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Interleukin-1beta
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NF-kappa B
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PEBP1 protein, human
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PIAS1 protein, human
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Phosphatidylethanolamine Binding Protein
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Protein Inhibitors of Activated STAT
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RNA, Messenger
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RNA, Small Interfering
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Recombinant Proteins
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Repressor Proteins
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STAT6 Transcription Factor
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STAT6 protein, human
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Small Ubiquitin-Related Modifier Proteins
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Interleukin-4
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Cyclooxygenase 2
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PTGS2 protein, human
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PRMT1 protein, human
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Protein-Arginine N-Methyltransferases