BACKGROUND AND AIMS: Studies have shown a decrease in key tight junction (TJ) proteins such as ZO-1 and occludin in both inflammatory bowel disease (IBD) and experimental models of inflammation. Our group has also shown an increase in claudin-1 in experimental colitis. METHODS: IEC-18 cells were treated with increasing doses of tumor necrosis factor alpha (TNFα). The TJ was assessed by transepithelial resistance (TER), permeability, Western blot, PCR, and immunofluorescence. Mucosal samples from patients with ulcerative colitis (UC), Crohn's disease (CD), and without IBD (normal) were assayed for TJ proteins occludin and claudin-1 by Western blot and a ratio of claudin-1 to occludin (C:O) was calculated. RESULTS: IEC-18 cells had increased permeability, decreased TER and an increase in claudin-1 with TNFα treatment. In human specimens, there was a decrease in occludin and an increase in claudin-1 leading to a significant increase in the C:O ratio in diseased UC colon compared to non-diseased UC colon (P < 0.001) and normal colon (P < 0.01). In CD, the C:O ratio was similar in all CD tissue irrespective of disease status. CONCLUSIONS: Treatment of IEC-18 cells with TNFα, a key inflammatory cytokine in IBD, led to a significant increase in claudin-1 expression. There was a significant increase in the C:O ratio in diseased colon in UC compared to the healthy appearing UC colon and normal controls. The C:O ratio was unchanged in CD despite presence or abscence of gross disease. This suggests that there may be an underlying difference in the TJ between UC and CD.
BACKGROUND AND AIMS: Studies have shown a decrease in key tight junction (TJ) proteins such as ZO-1 and occludin in both inflammatory bowel disease (IBD) and experimental models of inflammation. Our group has also shown an increase in claudin-1 in experimental colitis. METHODS: IEC-18 cells were treated with increasing doses of tumor necrosis factor alpha (TNFα). The TJ was assessed by transepithelial resistance (TER), permeability, Western blot, PCR, and immunofluorescence. Mucosal samples from patients with ulcerative colitis (UC), Crohn's disease (CD), and without IBD (normal) were assayed for TJ proteins occludin and claudin-1 by Western blot and a ratio of claudin-1 to occludin (C:O) was calculated. RESULTS: IEC-18 cells had increased permeability, decreased TER and an increase in claudin-1 with TNFα treatment. In human specimens, there was a decrease in occludin and an increase in claudin-1 leading to a significant increase in the C:O ratio in diseased UC colon compared to non-diseased UC colon (P < 0.001) and normal colon (P < 0.01). In CD, the C:O ratio was similar in all CD tissue irrespective of disease status. CONCLUSIONS: Treatment of IEC-18 cells with TNFα, a key inflammatory cytokine in IBD, led to a significant increase in claudin-1 expression. There was a significant increase in the C:O ratio in diseased colon in UC compared to the healthy appearing UC colon and normal controls. The C:O ratio was unchanged in CD despite presence or abscence of gross disease. This suggests that there may be an underlying difference in the TJ between UC and CD.
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