N-α-Benzoyl-N5-(2-Chloro-1-Iminoethyl)-l-Ornithine Amide, a Protein Arginine Deiminase Inhibitor, Reduces the Severity of Murine Collagen-Induced Arthritis

We evaluated whether N-a-benzoyl-N5-(2-chloro-1iminoethyl)-L-ornithine amide, a recently described pan-protein arginine deaminase inhibitor, could affect the development of arthritis and autoimmunity by treating mice in the collageninduced arthritis model with Cl-amidine on days 0–35

Van C. Willis

2011

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  • We hypothesized that if citrullination is an important mechanism in the pathogenesis of inflammatory arthritis, inhibition of protein arginine deaminase activity would lead to decreased disease severity because of reduced evolution of Abs to citrullinated protein Ags epitopes and autoantibody production
  • All of the mice developed disease, mice receiving daily i.p. injections of Clamidine in PBS, beginning on day 0, exhibited reduced clinical disease activity ∼50% on days 24–36. These results indicated that Cl-amidine treatment reduces clinical disease activity in collageninduced arthritis
  • Our data indicated that mice treated with Cl-amidine, a novel small molecule PAD inhibitor, exhibit a decrease in severity of clinical disease activity, as well as in joint inflammation and destruction in CIA
  • Cl-amidine treatment had no effect on collagen Ab-induced arthritis, suggesting that it does not alter the Ab-mediated effector phase of disease
  • Humoral response is not uniquely affected by Cl-amidine treatment. These results suggested that Cl-amidine treatment may exert broader effects on autoantibody responses than those resulting from decreased citrullinated epitope generation
  • It is possible that Cl-amidine treatment affects autoimmunity by inhibiting protein arginine deaminase activities unrelated to epitope generation or through effects on an unanticipated or unknown target(s), addressing these questions was beyond the scope of the current study

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