Factors Regulating the Effect of IL-4 on Intestinal Epithelial Barrier FunctionDi Leo V. · Yang P.-C. · Berin M.C. · Perdue M.H.
Intestinal Disease Research Programme, McMaster University, Hamilton, Ont., Canada
Background: Inflammatory bowel disease is associated with an imbalance in cytokine production and defective intestinal barrier function. Previous studies indicate that IL-4, a cytokine increased in food allergy and in early Crohn’s disease, enhances epithelial permeability. Here, we characterized the mechanism of action of IL-4 on cultured epithelial cells and examined if the anti-inflammatory cytokines, TGF-β or IL-10, can modulate the effects of IL-4. Methods: Confluent monolayers of human T84 epithelial cells were cultured with IL-4 alone or in combination with IL-10 or TGF-β or with inhibitors of protein synthesis and blockers of IL-4 receptor signalling pathways. Permeability was evaluated by measuring transepithelial resistance (TER), flux of 3H-fMLP (a small bacterial tripeptide) and horseradish peroxidase (HRP) (a macromolecule). Results: T84 cells cultured with IL-4 showed a significant drop in TER as well as an increased flux of 3H-fMLP and HRP. Co-treatment with IL-10 did not improve TER, whereas TGF-β attenuated the resistance drop. However, neither TGF-β nor IL-10 were able to correct the increased 3H-fMLP flux. In contrast, the increased HRP flux caused by IL-4 was inhibited by both IL-10 and TGF-β. TGF-β and IL-10 significantly reduced IL-4-enhanced values for endosomal area and paracellular spaces containing HRP. Inhibitor studies indicated the requirement for protein synthesis and the involvement of phosphatidylinositol 3-kinase. Conclusions: These results provide new insights into the regulation of intestinal barrier function and may suggest a novel approach in the treatment of intestinal inflammation.
© 2002 S. Karger AG, Basel
Correspondence to: Dr. M. Perdue
HSC-3N5C, McMaster University
1200 Main Street West, Hamilton, Ont. L8N3Z5 (Canada)
Tel. +1 905 525 9140/ext. 22585, Fax +1 905 522 3454
Received: Received: October 8, 2001
Accepted after revision: August 14, 2002
Number of Figures : 4, Number of Tables : 3, Number of References : 38
International Archives of Allergy and Immunology
Vol. 129, No. 3, Year 2002 (Cover Date: November 2002)
Journal Editor: D. Kraft, Vienna
ISSN: 1018–2438 (print), 1423–0097 (Online)
For additional information:http://www.karger.com/journals/iaa