Proteasome inhibitors to treat psoriasis

Psoriasis is a chronic skin inflammation that may involve bacterial superantigens, but the inflammatory mechanisms and T cell responses remain poorly understood. In March 1 Journal of Clinical Investigation Thomas Zollner and colleagues from JW Goethe University of Frankfurt, Germany, show that proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model.

Zollner et al. used human psoriatic skin tissue engrafted onto mice and observed that proteasome inhibition by PS-519 reduces superantigen-mediated T cell activation in vitro and in vivo. T cell proliferation was inhibited along with the expression of very early, early and late T cell activation molecules. In addition, expression of E-selectin ligands relevant for T cell homing to the skin was reduced, as was the binding to E-selectin in vitro (J Clin Invest 2002, 109:671-679.).

The authors concluded that these results, "suggest that PS-519 is an...