| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 159, Issue 6 2867-2876, Copyright © 1997 by American Association of Immunologists
ARTICLES |
DM Butler, AM Malfait, LJ Mason, PJ Warden, G Kollias, RN Maini, M Feldmann and FM Brennan
The Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom.
Arthritis spontaneously develops in mice expressing a human TNF-alpha transgene modified with the 3' untranslated region of beta-globin. We have backcrossed these mice onto the arthritis-susceptible DBA/1 background and found an acceleration of the onset of arthritis with successive generations of interbreeding. Bioactive TNF-alpha in primary synovial membrane cell cultures was significantly higher in the DBA/1 transgenic mice than in transgenic mice on the original background. Elevated levels of human TNF-alpha were accompanied by increases in synovial cell expression of murine IL-1beta and IL-6, but murine granulocyte-macrophage CSF, IFN-gamma, and IL-4 could not be detected. Interestingly, the anti-inflammatory cytokine IL-10 could be detected, but levels were not modulated by expression of the transgene. Analysis of the synovial membrane cell composition revealed that >50% of synovial cells were CD45-negative cells, presumably fibroblasts and endothelial cells, and the majority of CD45-expressing cells were neutrophils. Peritoneal macrophages and lymphocytes from the spleen, bone marrow, and lymph nodes required LPS stimulation to produce human TNF-alpha, indicating that, when activated, cells of these lineages were capable of expressing the transgene; however, few were found in synovial tissues. In contrast, fibroblasts derived from synovial tissue spontaneously released human TNF-alpha, and using immunohistochemical techniques, this cytokine was localized to fibroblast-like cells and chondrocytes. We propose that arthritis in DBA/1 human TNF-alpha transgenic mice is driven in part through the spontaneous expression of transgene by connective tissue cells, and there is little evidence of the participation of lymphocytes in this model.
This article has been cited by other articles:
|
|
 |
|
  D. E. Butz, G. Li, S. M. Huebner, and M. E. Cook A mechanistic approach to understanding conjugated linoleic acid's role in inflammation using murine models of rheumatoid arthritis Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R669 - R676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zwerina, K. Redlich, K. Polzer, L. Joosten, G. Kronke, J. Distler, A. Hess, N. Pundt, T. Pap, O. Hoffmann, et al. TNF-induced structural joint damage is mediated by IL-1 PNAS, July 10, 2007; 104(28): 11742 - 11747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Settembre, I. Annunziata, C. Spampanato, D. Zarcone, G. Cobellis, E. Nusco, E. Zito, C. Tacchetti, M. P. Cosma, and A. Ballabio Systemic inflammation and neurodegeneration in a mouse model of multiple sulfatase deficiency PNAS, March 13, 2007; 104(11): 4506 - 4511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Schubert, B. Maier, L. Morawietz, V. Krenn, and T. Kamradt Immunization with Glucose-6-Phosphate Isomerase Induces T Cell-Dependent Peripheral Polyarthritis in Genetically Unaltered Mice J. Immunol., April 1, 2004; 172(7): 4503 - 4509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C-Q Chu, Z Song, L Mayton, B Wu, and P H Wooley IFN{gamma} deficient C57BL/6 (H-2b) mice develop collagen induced arthritis with predominant usage of T cell receptor V{beta}6 and V{beta}8 in arthritic joints Ann Rheum Dis, October 1, 2003; 62(10): 983 - 990. [Abstract] [Full Text]
|
|
|
|
 |
|
 R A Mageed and D A Isenberg Tumour necrosis factor alpha in systemic lupus erythematosus and anti-DNA autoantibody production Lupus, December 1, 2002; 11(12): 850 - 855. [Abstract] [PDF]
|
|
|
|
|
|
C. Abad, C. Martinez, J. Leceta, R. P. Gomariz, and M. Delgado Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Collagen-Induced Arthritis: An Experimental Immunomodulatory Therapy J. Immunol., September 15, 2001; 167(6): 3182 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Wipke and P. M. Allen Essential Role of Neutrophils in the Initiation and Progression of a Murine Model of Rheumatoid Arthritis J. Immunol., August 1, 2001; 167(3): 1601 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Schrijver, M.-J. Melief, H. M. Markusse, I. Van Aelst, G. Opdenakker, M. P. Hazenberg, and J. D. Laman Peptidoglycan from sterile human spleen induces T-cell proliferation and inflammatory mediators in rheumatoid arthritis patients and healthy subjects Rheumatology, April 1, 2001; 40(4): 438 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O Williams, M. Feldmann, and R. N Maini Cartilage destruction and bone erosion in arthritis: the role of tumour necrosis factor alpha Ann Rheum Dis, November 1, 2000; 59(90001): i75 - 80. [Full Text] [PDF]
|
|
|
|
|
|
H. Schädlich, J. Ermann, M. Biskop, W. Falk, F. Sperling, A. Jüngel, J. Lehmann, F. Emmrich, and U. Sack Anti-inflammatory effects of systemic anti-tumour necrosis factor alpha treatment in human/murine SCID arthritis Ann Rheum Dis, July 1, 1999; 58(7): 428 - 434. [Abstract] [Full Text]
|
|
|
|
|
|
A.-M. Malfait, A. S. Malik, L. Marinova-Mutafchieva, D. M. Butler, R. N. Maini, and M. Feldmann The {beta}2-Adrenergic Agonist Salbutamol Is a Potent Suppressor of Established Collagen-Induced Arthritis: Mechanisms of Action J. Immunol., May 15, 1999; 162(10): 6278 - 6283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Malfait, R. Gallily, P. F. Sumariwalla, A. S. Malik, E. Andreakos, R. Mechoulam, and M. Feldmann From the Cover: The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis PNAS, August 15, 2000; 97(17): 9561 - 9566. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
