The cellular basis of adjuvant arthritis

Taurog, Joel D.; Sandberg, Gregory P.; Mahowald, Maren L.

doi:10.1016/0008-8749(83)90106-5

Cited by 104 publications

(16 citation statements)

References 22 publications

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“…AA can be induced in the inbred Lewis (LEW) (RT.1 l ) rat by subcutaneous immunization with heat-killed Mycobacterium tuberculosis H37Ra (Mtb), and it shares several features with human RA [13,14]. Furthermore, different phases of arthritis (incubation, onset, peak and recovery) during the course of AA are clearly identifiable [15,16], making it a suitable model for the study of preclinical (incubation phase) events in the disease course.…”

Section: Introductionmentioning

confidence: 99%

“…The induction of AA in LEW rats following Mtb injection involves the priming of potentially pathogenic T cells within the draining lymph nodes [14,25-28], and these T cells then migrate into the target organ, the joints, to initiate the development of arthritis. Conceivably, there are dynamic alterations in the relative frequency and activity of arthritogenic vs. disease-regulating T-cell subsets within the draining lymph nodes during the disease course.…”

Section: Introductionmentioning

confidence: 99%

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The gene expression profile of preclinical autoimmune arthritis and its modulation by a tolerogenic disease-protective antigenic challenge

Tan

et al. 2011

Arthritis Res Ther

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IntroductionAutoimmune inflammation is a characteristic feature of rheumatoid arthritis (RA) and other autoimmune diseases. In the natural course of human autoimmune diseases, it is rather difficult to pinpoint the precise timing of the initial event that triggers the cascade of pathogenic events that later culminate into clinically overt disease. Therefore, it is a challenge to examine the early preclinical events in these disorders. Animal models are an invaluable resource in this regard. Furthermore, considering the complex nature of the pathogenic immune events in arthritis, microarray analysis offers a versatile tool to define the dynamic patterns of gene expression during the disease course.MethodsIn this study, we defined the profiles of gene expression at different phases of adjuvant arthritis (AA) in Lewis rats and compared them with those of antigen mycobacterial heat shock protein 65 (Bhsp65)-tolerized syngeneic rats. Purified total RNA (100 ng) extracted from the draining lymph node cells was used to generate biotin-labeled fragment cRNA, which was then hybridized with an oligonucleotide-based DNA microarray chip. Significance analysis of microarrays was used to compare gene expression levels between the two different groups by limiting the false discovery rate to < 5%. Some of the data were further analyzed using a fold change ≥2.0 as the cutoff. The gene expression of select genes was validated by quantitative real-time PCR.ResultsIntriguingly, the most dramatic changes in gene expression in the draining lymphoid tissue ex vivo were observed at the preclinical (incubation) phase of the disease. The affected genes represented many of the known proteins that participate in the cellular immune response. Interestingly, the preclinical gene expression profile was significantly altered by a disease-modulating, antigen-based tolerogenic regimen. The changes mostly included upregulation of several genes, suggesting that immune tolerance suppressed disease by activating disease-regulating pathways. We identified a molecular signature comprising at least 12 arthritis-related genes altered by Bhsp65-induced tolerance.ConclusionsThis is the first report of microarray analysis in the rat AA model. The results of this study not only advance our understanding of the early phase events in autoimmune arthritis but also help in identifying potential targets for the immunomodulation of RA.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The gene expression profile of preclinical autoimmune arthritis and its modulation by a tolerogenic disease-protective antigenic challenge

Tan

et al. 2011

Arthritis Res Ther

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“…Antilymphocyte globulin suppresses the disease (13); moreover, W3/13 (anti-pan T) monoclonal antibodies, but not OX8 (anti-suppressor T) antibodies, do likewise (11). Perhaps most tellingly, the lesion may be passively transferred to naive animals by injection of T lymphoyctes from adjuvantinjected donors (14)(15)(16)(17). Given .observations such as these, we investigated the effects of the chimeric recombinant toxin IL2-PE40 (18)(19)(20) on modifying the course of adjuvant arthritis.…”

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confidence: 99%

Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats.

Case

Lorberboum-Galski

Lafyatis

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Adjuvant arthritis in rats is a T-cell dependent "autoimmune" disease with close similarities to several forms of human arthritis. Injection of mycobacterial adjuvant leads to T-cell activation and proliferation, processes in which the de novo expression of the interleukin 2 (IL-2) receptor plays a pivotal role. The subsequent massive mononudear cell infiltration of the joints ultimately results in complete joint destruction. Because activation of the helper/inducer subset of T lymphocytes is critical to the establishment of disease, we reasoned that EL2-PE4O, a cytotoxic IL-2-Pseudomonas exotoxin fusion protein that targets the membrane-penetration and ADP-ribosylation domains of the toxin to cells bearing the EL-2 receptor, would be an effective and specific therapy. Adjuvantinjected rats were randomized to treatment with EL2-PE4O, phosphate-buffered saline, or either of two control proteins related to IL2-PE40 but lacking either the receptor-binding moiety or an enzymatically active toxin domain and previously demonstrated to lack cytotoxicity in vitro. Intraperitoneal EL2-

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“…After week 4, a significant decrease in the number of mononuclear cells in the synovia was observed, corresponding to the chronic phases of AA [17, 26]. It is suggested that the activation of macrophages and helper T cells as well as the increase in the production of mediators is essential for the onset of AA [27]. In the present study, we found that administration of TJ-20 from day 0 or from day 7 (schedule I and II), but not from day 10 (schedule III), significantly suppressed the progress of AA.…”

Section: Discussionmentioning

confidence: 99%

Boi‐ogi‐to (TJ‐20), a Kampo Formula, Suppresses the Inflammatory Bone Destruction and the Expression of Cytokines in the Synovia of Ankle Joints of Adjuvant Arthritic Rats

Zhang

Liu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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TJ-20 is a formula consisting of 6 herbs that has been used in the clinical treatment of rheumatoid arthritis (RA) in China and Japan for centuries. However, scientific evidence of the effects of TJ-20 has not been established. In the present study, we focused on the therapeutic effects and investigated the main function of TJ-20 on adjuvant arthritis (AA), an animal model of RA, which was induced with complete Freund's adjuvant (CFA). TJ-20 was administered orally at 600 mg/kg once a day from 0, 7, and 10 days to 8 weeks after the CFA treatment. TJ-20 significantly ameliorated inflammatory progression and bone destruction in AA in a time-dependent manner. Furthermore, TJ-20 significantly reduced the increased changes in a number of macrophages and helper T cells. Moreover, TJ-20 suppressed the expression of TNF-α whereas it augmented the expression of IL-10 and attenuated Th1 cells responses in the synovia of the ankle joint. Therefore, TJ-20 regulated the expression of proinflammatory and anti-inflammatory cytokines in macrophages and Th1/Th2 balance in the synovia of ankle joints in AA rats. These results suggest the positive anti-inflammatory effect of TJ-20 and provide a scientific basis for the clinical use of TJ-20 for RA.

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The cellular basis of adjuvant arthritis

Cited by 104 publications

References 22 publications

The gene expression profile of preclinical autoimmune arthritis and its modulation by a tolerogenic disease-protective antigenic challenge

The gene expression profile of preclinical autoimmune arthritis and its modulation by a tolerogenic disease-protective antigenic challenge

Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats.

Boi‐ogi‐to (TJ‐20), a Kampo Formula, Suppresses the Inflammatory Bone Destruction and the Expression of Cytokines in the Synovia of Ankle Joints of Adjuvant Arthritic Rats

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