| First Author | Collins CB | Year | 2013 |
| Journal | Mucosal Immunol | Volume | 6 |
| Issue | 5 | Pages | 960-71 |
| PubMed ID | 23321985 | Mgi Jnum | J:315825 |
| Mgi Id | MGI:6831420 | Doi | 10.1038/mi.2012.134 |
| Citation | Collins CB, et al. (2013) Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function. Mucosal Immunol 6(5):960-71 |
| abstractText | Inflammatory bowel disease (IBD) is a chronic inflammatory condition thought to reflect a failure of the enteral immune system to adequately regulate itself. Inflammatory stress drives upregulation of heat-shock proteins (HSPs), including the pro-inflammatory chaperone, HSP90. This protein sequesters the transcription factor, heat-shock factor 1 (HSF1) in the cytoplasm preventing transcription of a number of anti-inflammatory proteins. We hypothesized that inhibition of HSP90 would exert an anti-inflammatory effect and thereby attenuate intestinal inflammation in murine models of IBD. Inhibition of HSP90 with 17-allylaminogeldanamycin (17-AAG) reduced inflammation in acute dextran sodium sulfate and chronic CD45RB(High) colitis models coinciding with increased interleukin (IL)-10 production in the colon. Regulatory T cells (Tregs) from mice treated with 17-AAG demonstrated significantly greater suppressive capacity in vitro abolished in HSF1-/- or IL-10-/- cells. Finally, Tregs treated with 17-AAG exhibited increased nuclear localization of HSF1 with resultant upregulation of HSF1 response genes, including HSP70, HSP90 and IL-10. |
