Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A2alpha (cPLA2alpha) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA2alpha plays a ke...

The signaling pathways utilized by naïve and experienced effector CD4 T cells during activation and proliferation were evaluated. While inhibition of either mTOR or MAPK alone was able to inhibit naïve T cell proliferation, both mTOR and MAPK (ERK) pathway inhibition was required to efficiently block experienced, effector CD4 T cell proliferation. This was demonstrated both in vitro, and in viv...

Animal models of rheumatoid arthritis (RA) are widely used for testing potential new therapies for RA. However, the question of which animal model is most predictive of therapeutic efficacy in human RA commonly arises in data evaluation. A retrospective review of the animal models used to evaluate approved, pending RA therapies, and compounds that were discontinued during phase II or III clinic...

Adjuvant arthritis (AA) in rats is susceptible to cell-mediated passive transfer. Collagen-induced arthritis (CIA) in rats is susceptible to passive transfer with antibody to type II collagen. We report here the development of strikingly severe arthritis in Lewis rats as the result of synergy between passively transferred antibody to type II collagen from rats with CIA and concanavalin A (Con A...

Background: Tamarixinin A, a natural tannin isolated from Myricaria bracteata, has been confirmed to have moderate anti-inflammatory effects in vitro and in vivo. However, how it effects rheumatoid arthritis (RA) is still unknown. Therefore, the aim of this study is to investigate the therapeutic effects of tamarixinin A on experimental RA, and explore the underlying mechanism. Methods: The ant...

Hospital data (Greenwood, 1968) and a population survey (to be published) suggest that rheumatoid arthritis is an uncommon disease in Western Nigeria. Furthermore, Nigerian patients satisfying the American Rheumatism Association criteria for a diagnosis of definite or probable rheumatoid arthritis (Ropes, Bennett, Cobb, Jacox, and Jessar, 1959) have a clinically milder disease than European pat...

Neutrophilic granulocytes and monocytes (granulomonocytic cells; GMC) drive the inflammatory process at the earliest stages of rheumatoid arthritis (RA). The migratory behavior and functional properties of GMC within the synovial tissue are, however, only incompletely characterized. Here we have analyzed GMC in the murine collagen-induced arthritis (CIA) model of RA using multi-photon real time...

Human leucocyte antigen (HLA) class II molecules have been shown to be associated with predisposition to rheumatoid arthritis (RA). We generated HLA-DR and DQ transgenic mice that lacked endogenous class II molecules to study the interaction between the DR and DQ molecules and define the immunologic mechanisms in rheumatoid arthritis. Using collagen-induced arthritis (CIA) as an experimental mo...

Two major T cell determinants are recognized by I-Ar-specific T cells in CII, the immunodominant CII610-618 (GPAGT AGA R) within CB10 and the subdominant CII445-453 (GPAGP AGE R) within CB8. Although the determinants differ by only two residues, CB8 is capable of inducing collagen-induced arthritis (CIA), while CB10 is not. We, therefore, investigated the structural differences between the two ...