caa a22 4500 445795700 CHVBK 20180317145124.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10620-011-1688-9 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1688-9 Increase in the Tight Junction Protein Claudin-1 in Intestinal Inflammation [Elektronische Daten] [Lisa Poritz, Leonard Harris III, Ashley Kelly, Walter Koltun] 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. Springer Science+Business Media, LLC, 2011 TNFα nationallicence Crohn's disease nationallicence Ulcerative colitis nationallicence Claudin-1 nationallicence Occludin nationallicence Poritz Lisa Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut Harris III Leonard Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut Kelly Ashley Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut Koltun Walter Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/10(2011-10-01), 2802-2809 0163-2116 56:10<2802 2011 56 10620 https://doi.org/10.1007/s10620-011-1688-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1688-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Poritz Lisa Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Harris III Leonard Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Kelly Ashley Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Koltun Walter Division of Colon and Rectal Surgery, Department of Surgery, The Milton S. Hershey Medical Center, H137, 500 University Drive, 17033, Hershey, PA, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/10(2011-10-01), 2802-2809 0163-2116 56:10<2802 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer