Immunopathogenesis of Arthritis in Mrl Mice

Pisetsky, David S.

Abstract

Autoimmune MRL-1pr mice develop an arthropathy with clinical and histological features in common with rheumatoid arthritis (RA). To elucidate the immunopathogenesis of this spontaneous disease model, it is proposed to identify effector mechanisms through genetic and cellular analysis. 1pr congenic mice and informative F1 and F2 generations will be studied to determine whether 1pr is itself sufficient for arthritis or requires interaction with other genes. To assess cellular mechanisms of disease, MRL- 1pr mice will be treated with various immunomodulatory agents such as monoclonal antibodies to L3T4 and Ia antigens. The nature of the cells infiltrating the synovium in both untreated and treated mice will then be investigated using immunohistologic techniques to characterize cell surface markers. The production of cytokines will also be evaluated in the synovium by in situ hybridization using probes for various mediators that have been postulated to promote joint changes. Finally, findings with MRL- 1pr mice will be compared with those observed in mice with collagen-induced arthritis, a model in which the role of T-cells is more defined. Together, these studies should help elucidate important facets of MRL-1pr arthritis and help assess its relationship to processes occurring in the RA joint.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Type: Specialized Center (P50)
• Project #: 5P50AR039162-05
• Application #: 3804437
• Support Year: 5
• Fiscal Year: 1991

Institution

• Name: Duke University
• DUNS #: 071723621
• City: Durham
• State: NC
• Country: United States
• Zip Code: 27705

Publications

Weinberg, J Brice; Lang, Thomas; Wilkinson, William E et al. (2006) Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures. Arthritis Res Ther 8:R140

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Elliott, Margaret K; Jarmi, Tambi; Ruiz, Phil et al. (2004) Effects of complement factor D deficiency on the renal disease of MRL/lpr mice. Kidney Int 65:129-38

Douglas, Glenn; Reilly, Christopher; Dooley, Mary Anne et al. (2004) Angiotensin-converting enzyme (insertion/deletion) and endothelial nitric oxide synthase polymorphisms in patients with systemic lupus erythematosus. J Rheumatol 31:1756-62

Erickson, G R; Northrup, D L; Guilak, F (2003) Hypo-osmotic stress induces calcium-dependent actin reorganization in articular chondrocytes. Osteoarthritis Cartilage 11:187-97

Oates, Jim C; Levesque, Marc C; Hobbs, Maurine R et al. (2003) Nitric oxide synthase 2 promoter polymorphisms and systemic lupus erythematosus in african-americans. J Rheumatol 30:60-7

Fermor, B; Weinberg, J B; Pisetsky, D S et al. (2002) Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthritis Cartilage 10:792-8

Fong, Alan M; Premont, Richard T; Richardson, Ricardo M et al. (2002) Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci U S A 99:7478-83

Guilak, Farshid; Erickson, Geoffrey R; Ting-Beall, H Ping (2002) The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes. Biophys J 82:720-7

Cernanec, Julie; Guilak, Farshid; Weinberg, J Brice et al. (2002) Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage. Arthritis Rheum 46:968-75