Please use this identifier to cite or link to this item:
Title: Integrin-linked kinase expression in myeloid cells promotes inflammatory signaling during experimental colitis
Authors: Ahmed, Afsar U;Yim, Howard CH;Alorro, Mariah;Ernst, Matthias;Williams, Bryan RG
Issue Date: 9-Aug-2017
EDate: 2017-08-09
Citation: Journal of Immunology 2017; online first: 9 August
Abstract: The pathology of inflammatory bowel diseases is driven by the inflammatory signaling pathways associated with mucosal epithelial damage. Myeloid cells are known to play an essential role in mediating epithelial inflammatory responses during injury. However, the precise role of these cells in stimulating intestinal inflammation and the subsequent tissue damage is unclear. In this article, we show that expression of integrin-linked kinase (ILK) in myeloid cells is critical for the epithelial inflammatory signaling during colitis induced by dextran sodium sulfate. Myeloid ILK (M-ILK) deficiency significantly ameliorates the pathology of experimental colitis. In response to dextran sodium sulfate, colonic infiltration of neutrophils and inflammatory cytokine production are impaired in M-ILK-deficient mice, and activation of epithelial NF-κB and PI3K signaling pathways are restricted by the M-ILK deficiency. In contrast, reduced epithelial damage in M-ILK-deficient mice is correlated with elevated levels of epithelial Stat3 activation and proliferation. Moreover, M-ILK-dependent inflammatory signaling in the mucosal epithelium can be therapeutically targeted by the pharmacological inhibition of ILK during experimental colitis. Collectively, these findings identify M-ILK as a critical regulator of epithelial inflammatory signaling pathways during colitis and, as a consequence, targeting M-ILK could provide therapeutic benefit.
DOI: 10.4049/jimmunol.1700125
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.

Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.