Administration of IL-18BP by gene therapy reduces inflammation and prevents joint destruction by downregulation of MMP-9 in rat AIA Role of MMP-9 in bone and joint destruction in arthritis

Details

Serval ID
serval:BIB_CCD817E4106D
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Administration of IL-18BP by gene therapy reduces inflammation and prevents joint destruction by downregulation of MMP-9 in rat AIA Role of MMP-9 in bone and joint destruction in arthritis
Title of the conference
3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society
Author(s)
Marotte H., Ahmed S., Amin M. A., Ruth J. H., Campbell P. L., Rabquer B. J., Lesch C., Lewis B. P., Dudler J., Koch A. E.
Address
Athens, Greece, May 07-11, 2011
ISBN
8756-3282
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
48
Series
Bone
Pages
S262-S263
Language
english
Notes
Publication type : Meeting Abstract
Abstract
Background and objectives: Interleukin-18 (IL-18) is a pleiotropic cytokine involved in rheumatoid arthritis (RA) pathogenesis. This studywas carried out to evaluate the efficicacy of interleukin-18 binding protein (IL-18BP) gene therapy in the rat adjuvant-induced arthritis (AIA) model and to decipher the mechanisms by which IL-18BP delivery lessens bone destruction. Materials and methods: Arthritis was induced in female Lewis rat by Mycobacterium butyricum and the mRNA expression of IL-18 and IL-18BP was determined in the joints. In a preventative study, rats were divided into an adenovirus producing IL-18BP-Fc (AdmIL-18BP-Fc) group (n=8) and an adenovirus producing green fluorescent protein (AdGFP) group (n=7). On day 8 after AIA induction, adenoviruses were injected. Clinical parameters were assessed. At day 18, during maximal arthritis, the rats were euthanized, ankles were collected, and X-rays were performed. mRNA and protein were extracted from joints for analyses by qRT-PCR, multiplex, Western blot, and zymography. Results: We observed a decrease in the [IL-18BP/IL-18] ratio from day 7 to day 45. Administration of AdmIL-18BPd-Fc decreased clinical parameters and prevented bone and joint destruction compared to AdGFP administration. IL-18BP delivery reduced the metalloproteinase 9 (MMP-9) levels by 33% (at protein level (Fig. 1B) and functional level (Fig. 1C) and the tartrate-resistant acid phosphatase (TRAP) level by 44% (Fig. 1D) in the joint homogenates from AdmIL-18BPd-Fc compared to AdGFP treated rats.However, no variationwas observed forMMP-2 at the protein level (Fig.1A) and functional level (Fig. 1C). Conclusions: In rat AIA, a decrease in the [IL-18BP/ IL-18] ratio was observed. IL-18BP delivery prevented joint and bone destruction by downregulating MMP-9 and TRAP, suggesting a potential benefit of a similar therapy in RA.
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Create date
17/05/2011 15:35
Last modification date
20/08/2019 16:47
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