Interleukin-1α, an Epithelial Danger Signal, Is a Potent Activator of Fibroblasts and Reactivator of Intestinal Inflammation.

Interleukin-1α, an Epithelial Danger Signal, Is a Potent Activator of Fibroblasts and Reactivator of Intestinal Inflammation.
Am J Pathol. 2015 Apr 9;
Authors: Scarpa M, Kessler S, Sadler T, West G, Homer C, McDonald C, de la Motte C, Fiocchi C, Stylianou E
Abstract
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-1α was released by injured colonocytes, thereby exacerbating 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-1α was the key IEC-derived necrotic cell product involved in HIF cytokine production. IL-1α-positive cells were identified in the epithelium in human IBD and dextran sulfate sodium (DSS)-induced colitis. IL-1α was detected in the stool of colitic mice before IL-1β. IL-1α enemas reactivated inflammation after DSS colitis recovery, induced IL-1 receptor expression in subepithelial fibroblasts, and induced de novo inflammation even in mice without overt colitis, after the administration of lo...

Source: The American Journal of Pathology - April 9, 2015 Category: Pathology Authors: Scarpa M, Kessler S, Sadler T, West G, Homer C, McDonald C, de la Motte C, Fiocchi C, Stylianou E Tags: Am J Pathol Source Type: research