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Induction of Experimental Arthritis by Borrelial Lipoprotein and CpG Motifs : Are Toll-Like Receptors 2, 4, 9 or CD-14 Involved?

Batsford, Stephen and Dunn, John and Mihatsch, Michael. (2011) Induction of Experimental Arthritis by Borrelial Lipoprotein and CpG Motifs : Are Toll-Like Receptors 2, 4, 9 or CD-14 Involved? The open rheumatology journal, Vol. 5. pp. 18-23.

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Official URL: http://edoc.unibas.ch/dok/A6004801

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Abstract

Bacterial lipoproteins and CpG-DNA are ligands for Toll-Like-Receptors (TLR) 2 and 9 respectively. Both classes of molecules were reported to induce experimental arthritis in rodents following direct intra-articular injection. Here we studied: 1) whether arthritis induction by Outer surface (Lipo)protein A (OspA) (B.burgdorferi) involved the TLR-2 as well as the TLR-4 or the CD-14 receptors in addition, and 2) re-examined the arthritogenic potential of CpG-DNA motifs in mice.Following intra-articular injection of the test substances [20µg recombinant, lipidated OspA; 1nM(6µg) to 10nM(60µg) synthetic CpG-DNA], inflammation was monitored by (99)Tc scintigraphy (ratio left/right knee joint uptake < 1.1 indicates inflammation) and by histology.Lipoprotein OspA induced severe, acute arthritis in TLR-2(+/+) w.t. but not in TLR-2(-/-) mice (p>0.01). There were no significant differences in the severity of arthritis induced in TLR-4(+/+) w.t. and TLR-4(-/-) mutant mice, or between CD14(+/+) w.t. and CD14(-/-) mice.CpG-DNA (1or 10 nM) did not cause notable inflammation in C57BL/6 mice; (99)Tc ratios were > 1.0 and histology showed only minimal changes.Induction of arthritis by the OspA lipoprotein of B.burgdorferi involves the TLR-2 receptor, no evidence for additional participation of TLR-4 or CD14 receptors was found. Intra-articular injection of CpG-DNA did not produce manifest joint injury in mice, at variance with previous reports.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Mihatsch, Michael J.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Bentham Open
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Feb 2014 15:45
Deposited On:27 Feb 2014 15:45

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