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Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2003 Jun; Vol. 132 (3), pp. 485-95. - Publication Year :
- 2003
-
Abstract
- Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-gamma and dexamethasone, whilst the pro-inflammatory cytokine TNF-alpha had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins.
- Subjects :
- Arthritis, Rheumatoid immunology
Arthritis, Rheumatoid pathology
Blood Proteins genetics
Blood Proteins metabolism
Cell Line
Complement C3b Inactivator Proteins
Complement Factor H genetics
Complement Factor H metabolism
Cytotoxicity, Immunologic
Gene Expression
Humans
Promoter Regions, Genetic
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Synovial Membrane immunology
Synovial Membrane pathology
Transfection
Tumor Cells, Cultured
Arthritis, Rheumatoid metabolism
Blood Proteins physiology
Complement Factor H physiology
Fibroblasts metabolism
Synovial Membrane metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0009-9104
- Volume :
- 132
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 12780697
- Full Text :
- https://doi.org/10.1046/j.1365-2249.2003.02173.x