Abstract | OBJECTIVE: METHODS: The potential role of the alpha7nAChR in modulating proinflammatory cytokine expression in fibroblast-like synoviocytes (FLS) was identified by screening an adenoviral short hairpin RNA (Ad. shRNA) library. An alpha7-specific antibody was used for immunohistochemistry, and fluorescein isothiocyanate-labeled alpha-bungarotoxin, which binds specifically to the alpha7nAChR, was used for immunofluorescence. Gene expression in FLS was determined by quantitative polymerase chain reaction with primers specific for the alpha7nAChR. In addition, we analyzed messenger RNA ( mRNA) expression of dupalpha7, a variant alpha7 transcript. Next, we studied the functional role of the alpha7nAChR in RA FLS by examining the effects of alpha7-specific agonists on the production of interleukin-6 (IL-6) and IL-8 by activated FLS. RESULTS: CONCLUSION: The alpha7nAChR and its dupalpha7 variant are expressed in RA synovium, where they may play a critical role in regulating inflammation. Targeting the alpha7nAChR could provide a novel antiinflammatory approach to the treatment of RA.
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Authors | Marjolein A van Maanen, Susanne P Stoof, Esmerij P van der Zanden, Wouter J de Jonge, Richard A Janssen, David F Fischer, Nick Vandeghinste, Reginald Brys, Margriet J Vervoordeldonk, Paul P Tak |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 60
Issue 5
Pg. 1272-81
(May 2009)
ISSN: 0004-3591 [Print] United States |
PMID | 19404936
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chrna7 protein, human
- Interleukin-6
- Interleukin-8
- Neurotransmitter Agents
- RNA, Messenger
- Receptors, Nicotinic
- alpha7 Nicotinic Acetylcholine Receptor
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Topics |
- Arthritis, Rheumatoid
(physiopathology)
- Cells, Cultured
- Fibroblasts
(physiology)
- Humans
- Immunohistochemistry
- Interleukin-6
(biosynthesis)
- Interleukin-8
(biosynthesis)
- Neurotransmitter Agents
(physiology)
- Polymerase Chain Reaction
- RNA, Messenger
(analysis)
- Receptors, Nicotinic
(analysis, physiology)
- Synovial Membrane
(chemistry, cytology)
- alpha7 Nicotinic Acetylcholine Receptor
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