Impaired Sensitivity to Fas-Induced Apoptosis of Lymphocytes in Ulcerative Colitis Lesions

Abstract

We have previously reported that lamina propria lymphocytes (LPLs) in ulcerative colitis lesions express Fas ligand (FasL), suggesting that Fas/FasL-induced apoptosis participates in the mucosal damage of ulcerative colitis (UC). The aim of this study was to examine the sensitivity of Fas-mediated apoptosis in LPLs to analyze if down-regulation of LPL expansion is impaired. The sensitivity of Fas-mediated apoptosis of LPLs from UC, Crohn’s disease (CD), and controls were examined by flow cytometry. Activation of NF-κB in LPLs was analyzed by immunohistochemistry and the electrophoretic mobility shift assay. The effect of NF-κB on the sensitivity of apoptosis in LPLs was examined with pyrrolidine dithiocarbamate and NF-?B decoy oligodeoxynucleotide. LPLs from UC and CD lesions, especially UC, showed decreased sensitivity of apoptosis. NF-κB was activated in LPLs from UC lesions. Inhibition of NF-κB activation increased apoptosis in UC LPLs. It is concluded that UC LPLs were resistant to Fas-mediated apoptosis, and activation of NF-κB was involved in the mechanism.