دورية أكاديمية
Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis.
العنوان: | Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis. |
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المؤلفون: | Makrygiannakis D; Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, SE- 141 86, Stockholm, Sweden., Revu S, Engström M, af Klint E, Nicholas AP, Pruijn GJ, Catrina AI |
المصدر: | Arthritis research & therapy [Arthritis Res Ther] 2012 Jan 27; Vol. 14 (1), pp. R20. Date of Electronic Publication: 2012 Jan 27. |
نوع المنشور: | Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101154438 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-6362 (Electronic) Linking ISSN: 14786354 NLM ISO Abbreviation: Arthritis Res Ther Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, 2003- |
مواضيع طبية MeSH: | Antirheumatic Agents/*therapeutic use , Arthritis, Rheumatoid/*drug therapy , Citrulline/*metabolism , Glucocorticoids/*therapeutic use , Synovial Membrane/*drug effects, Adult ; Aged ; Aged, 80 and over ; Antirheumatic Agents/administration & dosage ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/pathology ; Dexamethasone/administration & dosage ; Dexamethasone/therapeutic use ; Double-Blind Method ; Female ; Glucocorticoids/administration & dosage ; Humans ; Hydrolases/metabolism ; Immunohistochemistry ; Injections, Intra-Articular ; Male ; Methotrexate/administration & dosage ; Methotrexate/therapeutic use ; Middle Aged ; Peptides/metabolism ; Protein-Arginine Deiminase Type 2 ; Protein-Arginine Deiminase Type 4 ; Protein-Arginine Deiminases ; Synovial Membrane/metabolism ; Synovial Membrane/pathology ; Time Factors ; Tissue Culture Techniques ; Treatment Outcome ; Triamcinolone Acetonide/administration & dosage ; Triamcinolone Acetonide/analogs & derivatives ; Triamcinolone Acetonide/therapeutic use |
مستخلص: | Introduction: Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination. Methods: Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intraarticular glucocorticoid injection, and eight healthy volunteers. Synovial inflammation was assessed with double-blind semiquantitative analysis of lining thickness, cell infiltration, and vascularity by using a 4-point scale. Expression of citrullinated proteins (CPs) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically with double-blind semiquantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB), mononuclear cells (MCs), and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed with immunohistochemistry for expression of CP as well as PAD2 and PAD4 enzymes. Results: The presence of synovial CP was almost exclusive in RA compared with healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination, as demonstrated by the decrease in the level of citrullination and PAD expression after incubation of SFMC and synovial explants with dexamethasone. Conclusion: Synovial citrullination and PAD expression are dependent on local inflammation and targeted by glucocorticoids. |
التعليقات: | Comment in: Arthritis Res Ther. 2012;14(1):108. (PMID: 22380578) |
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المشرفين على المادة: | 0 (Antirheumatic Agents) 0 (Glucocorticoids) 0 (Peptides) 29VT07BGDA (Citrulline) 7S5I7G3JQL (Dexamethasone) EC 3.- (Hydrolases) EC 3.5.3.15 (PADI2 protein, human) EC 3.5.3.15 (PADI4 protein, human) EC 3.5.3.15 (Protein-Arginine Deiminase Type 2) EC 3.5.3.15 (Protein-Arginine Deiminase Type 4) EC 3.5.3.15 (Protein-Arginine Deiminases) F446C597KA (Triamcinolone Acetonide) I7GT1U99Y9 (triamcinolone hexacetonide) YL5FZ2Y5U1 (Methotrexate) |
تواريخ الأحداث: | Date Created: 20120131 Date Completed: 20121217 Latest Revision: 20211021 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC3392813 |
DOI: | 10.1186/ar3702 |
PMID: | 22284820 |
قاعدة البيانات: | MEDLINE |
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