hymecromone and salubrinal

The ability to modulate direct MHC class I (MHC I) Ag presentation is a desirable goal for the treatment of a variety of conditions, including autoimmune diseases, chronic viral infections, and cancers. It is therefore necessary to understand how changes in the cellular environment alter the cells' ability to present peptides to T cells. The unfolded protein response (UPR) is a signaling pathway activated by the presence of excess unfolded proteins in the endoplasmic reticulum. Previous studies have indicated that chemical induction of the UPR decreases direct MHC I Ag presentation, but the precise mechanisms are unknown. In this study, we used a variety of small molecule modulators of different UPR signaling pathways to query which UPR signaling pathways can alter Ag presentation in both murine and human cells. When signaling through the PERK pathway, and subsequent eIF2α phosphorylation, was blocked by treatment with GSK2656157, MHC I Ag presentation remain unchanged, whereas treatment with salubrinal, which has the opposite effect of GSK2656157, decreases both Ag presentation and overall cell-surface MHC I levels. Treatment with 4μ8C, an inhibitor of the IRE1α UPR activation pathway that blocks splicing of

Topics: Adenine; Animals; Antigen Presentation; Cell Line; Cinnamates; Endoribonucleases; Eukaryotic Initiation Factor-2; Humans; Hymecromone; Indoles; Mice; Phosphorylation; Protein Serine-Threonine Kinases; RNA, Messenger; Signal Transduction; Thiourea; Unfolded Protein Response; X-Box Binding Protein 1