IL-8 secretion and neutrophil activation by HT-29 colonic epithelial cells

Abstract

This study examines the ability of HT-29 human colonic epithelial cells to stimulate neutrophil migration and adhesion. Interleukin-8 (IL-8), a potent neutrophil chemoattractant, was detected in conditioned media from both unstimulated (1.1 ng/ml) and IL-1 beta-stimulated (16.1 ng/ml) HT-29 cultures. Conditioned medium from IL-1 beta-exposed HT-29 cells stimulated neutrophil migration (395% of control, P < 0.01), and this effect was completely inhibited by anti-IL-8 antibody. HT-29 medium also induced shedding of neutrophil L-selectin and increased expression of neutrophil CD11/CD18 adhesion receptors. Coculture of HT-29 cells with human endothelial cell monolayers resulted in increased neutrophil transendothelial migration (169% of control, P < 0.01), which was blocked by both anti-IL-8 and anti-CD18 antibody. Northern hybridization analysis demonstrated increased levels of mRNA for IL-8 and intercellular adhesion molecule-1 (ICAM-1) in cytokine-treated HT-29 cells. Cytokine stimulation of HT-29 monolayers was also associated with increased neutrophil adhesion to these cells. Neutrophil-HT-29 cell adhesion was blocked by monoclonal antibodies to neutrophil CD18 or to ICAM-1 on the HT-29 cells (86% and 56% inhibition, respectively, P < 0.01 for both). These data suggest that IL-8 secretion by activated colonic epithelial cells may contribute to neutrophil extravasation and tissue infiltration in intestinal inflammation.

Campylobacter-Induced Interleukin-8 Secretion in Polarized Human Intestinal Epithelial Cells RequiresCampylobacter-Secreted Cytolethal Distending Toxin- and Toll-Like Receptor-Mediated Activation of NF-κB

“…IL-8 chemoattracts neutrophils to infection sites, initiating local inflammation (29,31). It has been reported previously that the interaction of enteric pathogens, including Campylobacter, with T84 polarized human intestinal epithelial cells increases IL-8 secretion (5,9,37,50).…”

Non-Small Cell Lung Cancer Cells Induce Monocytes to Increase Expression of Angiogenic Activity

“…The source(s) of angiogenic factor expression within NSCLC have not been completely elucidated. Malignant cells can and do produce angiogenic factors (22,32) A number of different cell types contribute to angiogenesis, including cancer cells (12,34), endothelial cells (35)(36)(37), fibroblasts (13,15), eosinophils (38), platelets (39), and monocyte-derived macrophages (40 -42). Each cell type displays a certain repertoire of angiogenic factors, depending on the stimulus.…”

“…Conversely, in malignancy, there is a predominance of angiogenic factors or a relative decrease in angiostatic factors tipping the balance in favor of neovascularization (6, 9 -11). The cell type(s) that affect the balance of angiogenic factors may be the malignant cells (12,13) or the tumor stroma (14,15).…”

ZBP-89, Sp1, and Nuclear Factor-κB Regulate Epithelial Neutrophil-activating Peptide-78 Gene Expression in Caco-2 Human Colonic Epithelial Cells

“…A wide variety of cell types can release IL-8 if stimulated appropriately; however, it is produced mainly by activated monocytes/macrophages and endothelial cells and to a lesser extent by neutrophils and epithelial cells (2,10,(12)(13)(14).…”