Abstract | OBJECTIVE: METHODS: Expression of NOD-2 in synovial tissues was analyzed by immunohistochemistry. Expression and induction of NOD-2 in RA synovial fibroblasts (RASFs) were measured by conventional and real-time polymerase chain reaction (PCR) analyses. Levels of interleukin-6 (IL-6) and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA) and expression of matrix metalloproteinases ( MMPs) by ELISA and/or real-time PCR. NOD-2 expression was silenced with small interfering RNA. Western blotting with antibodies against phosphorylated and total p38, JNK, and ERK, as well as inhibitors of p38, JNK, and ERK was performed. Activation of NF-kappaB was measured by electrophoretic mobility shift assay. RESULTS: CONCLUSION: Not only TLRs, but also the PRR NOD-2 is expressed in the synovium of RA patients, and activation of NOD-2 acts synergistically with TLRs in the production of proinflammatory and destructive mediators. Therefore, NOD-2 might contribute to the initiation and perpetuation of chronic, destructive inflammation in RA.
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Authors | Caroline Ospelt, Fabia Brentano, Astrid Jüngel, Yvonne Rengel, Christoph Kolling, Beat A Michel, Renate E Gay, Steffen Gay |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 60
Issue 2
Pg. 355-63
(Feb 2009)
ISSN: 0004-3591 [Print] United States |
PMID | 19180502
(Publication Type: Journal Article)
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Chemical References |
- IL6 protein, human
- Interleukin-6
- Interleukin-8
- Lipopolysaccharides
- NF-kappa B
- NOD2 protein, human
- Nod2 Signaling Adaptor Protein
- RNA, Messenger
- RNA, Small Interfering
- Toll-Like Receptors
- Tumor Necrosis Factor-alpha
- Acetylmuramyl-Alanyl-Isoglutamine
- Matrix Metalloproteinases
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Topics |
- Acetylmuramyl-Alanyl-Isoglutamine
(metabolism, pharmacology)
- Arthritis, Rheumatoid
(metabolism, pathology)
- Cells, Cultured
- Fibroblasts
(drug effects, metabolism, pathology)
- Gene Expression
(drug effects)
- Gene Silencing
- Humans
- Interleukin-6
(metabolism)
- Interleukin-8
(metabolism)
- Lipopolysaccharides
(pharmacology)
- Matrix Metalloproteinases
(genetics, metabolism)
- NF-kappa B
(biosynthesis)
- Nod2 Signaling Adaptor Protein
(genetics, metabolism)
- RNA, Messenger
(drug effects, metabolism)
- RNA, Small Interfering
(metabolism)
- Signal Transduction
- Synovial Membrane
(drug effects, metabolism, pathology)
- Toll-Like Receptors
(metabolism)
- Tumor Necrosis Factor-alpha
(pharmacology)
- Up-Regulation
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