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Interleukin‐18 disrupts tight junctions in gastric and intestinal epithelial monolayers
Author(s) -
Lapointe Tamia K,
Hirota Christina L,
Menard Daniel,
MacNaughton Wallace K,
Buret Andre G
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.348.6
Subject(s) - occludin , tight junction , barrier function , proinflammatory cytokine , claudin , matrix metalloproteinase , cell junction , chemistry , immunology , inflammation , biology , microbiology and biotechnology , medicine , cell , biochemistry
Chronic inflammatory conditions of the gut including Helicobacter pylori gastritis and the inflammatory bowel diseases ulcerative colitis and Crohn's disease are characterized by compromised epithelial barrier function and tight junction alterations. Both conditions are associated with increased mucosal levels of the proinflammatory cytokine interleukin‐18 (IL‐18). The role of IL‐18 in epithelial barrier defects has yet to be investigated. AIM This study assessed the effect of IL‐18 on gastric and intestinal epithelial barrier structure and function. RESULTS Human gastric (HGE‐20) and colonic (Caco‐2) epithelial monolayers challenged with IL‐18 showed redistribution of tight junctional proteins claudin‐4 and occludin. This was accompanied by a matrix metalloproteinase‐9 independent decrease in claudin‐4 and occludin expression. Despite disrupting epithelial tight junction structure, IL‐18 treatment did not affect apical‐to‐basolateral fluxes of 3000MW FITC‐dextran, suggesting no effect of IL‐18 on transepithelial permeability to small molecules. CONCLUSION These findings demonstrate that IL‐18 disrupts epithelial barrier structure in gastric and intestinal monolayers without affecting transepithelial permeability. Future studies will assess the significance of IL‐18 ‐mediated tight junction disruption with respect to leukocyte transmigration across epithelia. Funded by CIHR.