Upregulation of citrullination pathway: From Autoimmune to Idiopathic Lung Fibrosis

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Title: Upregulation of citrullination pathway: From Autoimmune to Idiopathic Lung Fibrosis
Author(s): Samara, KD
Trachalaki, A
Tsitoura, E
Koutsopoulos, AV
Lagoudaki, ED
Lasithiotaki, I
Margaritopoulos, G
Pantelidis, P
Bibaki, E
Siafakas, NM
Tzanakis, N
Wells, AU
Antoniou, KM
Item Type: Journal Article
Abstract: Background: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. Methods: We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. Results: PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in all groups, with the strongest cytoplasmic expression observed in granulocytes in RA-ILD and IPF. PADI2 mRNA and immunostaining of BAL cells, were similar in all groups among smokers. Overall, stronger staining was observed in current smokers. Citrullinated peptides were significantly increased in IPF compared to RA-ILD and controls. In RA-ILD, protein citrullination strongly correlated with PADI4 expression and anti-citrullinated protein antibodies (ACPAs). Conclusions: These results suggest that the citrullination pathway is upregulated in IPF and in RA-ILD.
Publication Date: 29-Dec-2017
Date of Acceptance: 2-Dec-2017
URI: http://hdl.handle.net/10044/1/56199
DOI: https://dx.doi.org/10.1186/s12931-017-0692-9
ISSN: 1465-9921
Publisher: BioMed Central
Journal / Book Title: Respiratory Research
Volume: 18
Copyright Statement: © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology
Life Sciences & Biomedicine
Respiratory System
Citrullination
Peptidylarginine deiminases
Smoking
Idiopathic pulmonary fibrosis
Rheumatoid arthritis
Interstitial lung disease
Pathogenesis
NEUTROPHIL EXTRACELLULAR TRAPS
RHEUMATOID-ARTHRITIS
PULMONARY-FIBROSIS
EXTRAARTICULAR MANIFESTATIONS
DISEASE
EXPRESSION
AUTOANTIBODIES
ASSOCIATION
ANTIBODIES
DEIMINASES
Citrullination
Idiopathic pulmonary fibrosis
Interstitial lung disease
Pathogenesis
Peptidylarginine deiminases
Rheumatoid arthritis
Smoking
Science & Technology
Life Sciences & Biomedicine
Respiratory System
Citrullination
Peptidylarginine deiminases
Smoking
Idiopathic pulmonary fibrosis
Rheumatoid arthritis
Interstitial lung disease
Pathogenesis
NEUTROPHIL EXTRACELLULAR TRAPS
RHEUMATOID-ARTHRITIS
PULMONARY-FIBROSIS
EXTRAARTICULAR MANIFESTATIONS
DISEASE
EXPRESSION
AUTOANTIBODIES
ASSOCIATION
ANTIBODIES
DEIMINASES
1102 Cardiovascular Medicine And Haematology
1103 Clinical Sciences
Respiratory System
Publication Status: Published
Article Number: 218
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