pr-957 and Purpura--Thrombocytopenic--Idiopathic

The immunoproteasome, a special isoform of the 20S proteasome, is expressed when the cells receive an inflammatory signal. Immunoproteasome inhibition proved efficacy in the treatment of autoimmune diseases. However, the role of the immunoproteasome in the pathogenesis of immune thrombocytopenia (ITP) remains unknown. We found that the expression of the immunoproteasome catalytic subunit, large multifunctional protease 2 (LMP2), was significantly upregulated in peripheral blood mononuclear cells of active ITP patients compared to those of healthy controls. No significant differences in LMP7 expression were observed between patients and controls. ML604440, an specific LMP2 inhibitor, had no significant impact on the platelet count of ITP mice, while ONX-0914 (an inhibitor of both LMP2 and LMP7) increased the number of platelets.

Topics: Adolescent; Adult; Aged; Animals; Case-Control Studies; Cysteine Endopeptidases; Disease Models, Animal; Female; Humans; Lymphocyte Activation; Macrophages; Male; Mice, Inbred C57BL; Middle Aged; Oligopeptides; Phagocytosis; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Purpura, Thrombocytopenic, Idiopathic; Receptors, IgG; Signal Transduction; T-Lymphocytes; Young Adult