Activation of Peptidylarginine Deiminase in the Salivary Glands of Balb/c Mice Drives the Citrullination of Ro and La Ribonucleoproteins

Autor: Rafael Herrera-Esparza, Esperanza Avalos-Díaz, J. D. Murillo-Vazquez, Juan-José Bollain y Goytia, Mayra Rodríguez-Rodríguez, Deyanira Pacheco-Tovar, María-Elena Pérez-Pérez, Guadalupe Pacheco-Tovar
Jazyk: angličtina
Rok vydání: 2017
Předmět:
lcsh:Immunologic diseases. Allergy
0301 basic medicine
Lipopolysaccharides
Arginine
Article Subject
Ductal cells
Hydrolases
Immunology
Apoptosis
Biology
Autoantigens
Salivary Glands
BALB/c
03 medical and health sciences
Mice
0302 clinical medicine
Adenosine Triphosphate
Western blot
Protein-Arginine Deiminase Type 4
Protein-Arginine Deiminase Type 2
medicine
Immunology and Allergy
Animals
Humans
Cells
Cultured
Ribonucleoprotein
Mice
Inbred BALB C
medicine.diagnostic_test
Citrullination
Fibrinogen
General Medicine
biology.organism_classification
Molecular biology
In vitro
Enzyme Activation
030104 developmental biology
Sjogren's Syndrome
Gene Expression Regulation
Ribonucleoproteins
Protein-Arginine Deiminases
Protein-Arginine Deiminase Type-4
Cytokines
Inflammation Mediators
lcsh:RC581-607
030215 immunology
Research Article
Zdroj: Journal of Immunology Research
Journal of Immunology Research, Vol 2017 (2017)
ISSN: 2314-8861
DOI: 10.1155/2017/8959687
Popis: The goal of the present study was to determine whether peptidylarginine deiminase PAD2 and PAD4 enzymes are present in Balb/c mouse salivary glands and whether they are able to citrullinate Ro and La ribonucleoproteins. Salivary glands from Balb/c mice were cultured in DMEM and supplemented with one of the following stimulants: ATP, LPS, TNF, IFNγ, or IL-6. A control group without stimulant was also evaluated. PAD2, PAD4, citrullinated peptides, Ro60, and La were detected by immunohistochemistry and double immunofluorescence. PAD2 and PAD4 mRNAs and protein expression were detected by qPCR and Western blot analysis. PAD activity was assessed using an antigen capture enzyme-linked immunosorbent assay. LPS, ATP, and TNF triggered PAD2 and PAD4 expression; in contrast, no expression was detected in the control group (p<0.001). PAD transcription slightly increased in response to stimulation. Additionally, PAD2/4 activity modified the arginine residues of a reporter protein (fibrinogen) in vitro. PADs citrullinated Ro60 and La ribonucleoproteins in vivo. Molecular stimulants induced apoptosis in ductal cells and the externalization of Ro60 and La ribonucleoproteins onto apoptotic membranes. PAD enzymes citrullinate Ro and La ribonucleoproteins, and this experimental approach may facilitate our understanding of the role of posttranslational modifications in the pathophysiology of Sjögren’s syndrome.
Databáze: OpenAIRE
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