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Intra-articular fms...
Intra-articular fms-like tyrosine kinase 3 ligand expression is a driving force in induction and progression of arthritis.
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- Dehlin, Mats, 1968 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,University of Gothenburg, Sweden
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- Bokarewa, Maria, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,University of Gothenburg, Sweden
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- Rottapel, Robert (författare)
- University of Toronto, Canada
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- Foster, Simon J (författare)
- University of Sheffield, England
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- Magnusson, Mattias, 1972 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,University of Gothenburg, Sweden
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- Dahlberg, Leif E (författare)
- University Hospital UMAS, Malmo, Sweden
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- Tarkowski, Andrej, 1951 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,University of Gothenburg, Sweden
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(creator_code:org_t)
- 2008-11-04
- 2008
- Engelska.
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:11
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https://liu.diva-por... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND: One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). CONCLUSIONS/SIGNIFICANCE: Our findings indicate that Flt3-L is strongly expressed at the site of inflammation in human RA. It exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. Owing to these properties, treatment attempts to neutralize this molecule should be considered in RA.
Nyckelord
- Adjuvants
- Immunologic
- Adult
- Aged
- Aged
- 80 and over
- Animals
- Arthritis
- Rheumatoid
- immunology
- pathology
- B-Lymphocytes
- immunology
- transplantation
- Bacterial Proteins
- administration & dosage
- immunology
- Disease Models
- Animal
- Disease Progression
- Female
- Humans
- Injections
- Intra-Articular
- Knee Joint
- immunology
- pathology
- Male
- Membrane Proteins
- blood
- immunology
- Mice
- Mice
- Inbred BALB C
- Middle Aged
- Peptidoglycan
- administration & dosage
- immunology
- Synovial Fluid
- immunology
- Young Adult
- MEDICINE
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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