| First Author | Scarpa M | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 6 | Pages | 1624-37 |
| PubMed ID | 25864926 | Mgi Jnum | J:221178 |
| Mgi Id | MGI:5638464 | Doi | 10.1016/j.ajpath.2015.02.018 |
| Citation | Scarpa M, et al. (2015) The Epithelial Danger Signal IL-1alpha Is a Potent Activator of Fibroblasts and Reactivator of Intestinal Inflammation. Am J Pathol 185(6):1624-37 |
| abstractText | Intestinal epithelial cell (IEC) death is typical of inflammatory bowel disease (IBD). We investigated: i) whether IEC-released necrotic cell products (proinflammatory mediators) amplify mucosal inflammation, ii) the capacity of necrotic cell lysates from HT29 cells or human IECs to induce human intestinal fibroblasts' (HIF) production of IL-6 and IL-8, and iii) whether IL-1alpha, released by injured colonocytes, exacerbated experimental IBD. Necrotic cell lysates potently induced HIF IL-6 and IL-8 production independent of Toll-like receptors 2 and 4, receptor for advanced glycation end-products, high-mobility group box 1, uric acid, IL-33, or inflammasome activation. IL-1alpha was the key IEC-derived necrotic cell product involved in HIF cytokine production. IL-1alpha-positive cells were identified in the epithelium in human IBD and dextran sulfate sodium (DSS)-induced colitis. IL-1alpha was detected in the stool of colitic mice before IL-1beta. IL-1alpha enemas reactivated inflammation after DSS colitis recovery, induced IL-1 receptor expression in subepithelial fibroblasts, and activated de novo inflammation even in mice without overt colitis, after the administration of low-dose DSS. IL-1alpha amplifies gut inflammation by inducing cytokine production by mesenchymal cells. IL-1alpha-mediated IEC-fibroblast interaction may be involved in amplifying and perpetuating inflammation, even without obvious intestinal damage. IL-1alpha may be a target for treating early IBD or preventing the reactivation of IBD. |
