Fig. 5: Hypoxia-induced switch in the phenotype of proteasome from 26S to immunoproteasome leads to upregulation and activation of HLA-DRα in MSCs. | Cell Death & Disease

Fig. 5: Hypoxia-induced switch in the phenotype of proteasome from 26S to immunoproteasome leads to upregulation and activation of HLA-DRα in MSCs.

From: Hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of mesenchymal stem cells

Fig. 5

a Human bone marrow-derived MSCs were treated with 26S proteasome inhibitor (MG132, 2 μM and 5 μM) for 24 h. Western blot analysis revealed a significant increase in HLA-DRα protein levels in 26S proteasome inhibited normoxic MSCs; n = 3. b, c MSCs were incubated in hypoxia chamber with or without immunoproteasome inhibitor (Onx0914 1 µM for 4 h). Next, co-immunoprecipitation assay was performed in cell lysates to measure- the binding between HLA-DRα and invariant chain- Ii/CD74 (to measure the levels of immature HLA-DRα, or antigen unloaded HLA-DRα); and the binding between HLA-DRα and HLA-DM (to measure levels of activated HLA-DRα, or antigen loaded HLA-DRα). Inhibition of immunoproteasome increased the binding between HLA-DRα and Ii/CD74; and decreased the binding between HLA-DRα and HLA-DM in hypoxic MSCs; n = 3. *p < 0.05 compared to normoxic MSCs, #p < 0.05 compared to hypoxic MSCs. Each experiment was repeated 3–4 times.

Back to article page