Toll-like receptor-mediated responses of primary intestinal epithelial cells during the development of colitis
Singh, J.C.I. Cruickshank, S.M. Newton, D.J. Wakenshaw, L. Lan, J. Lodge, J.P.A. Felsburg, P.J. Carding, S.R.
Singh, J.C.I.
Cruickshank, S.M.
Newton, D.J.
Wakenshaw, L.
Lan, J.
Lodge, J.P.A.
Felsburg, P.J.
Carding, S.R.
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2004
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Abstract
The interleukin-2-deficient (IL-2¿/¿) mouse model of ulcerative colitis was used to test the hypothesis that colonic epithelial cells (CEC) directly respond to bacterial antigens and that alterations in Toll-like receptor (TLR)-mediated signaling may occur during the development of colitis. TLR expression and activation of TLR-mediated signaling pathways in primary CEC of healthy animals was compared with CEC in IL-2¿/¿ mice during the development of colitis. In healthy animals, CEC expressed functional TLR, and in response to the TLR4 ligand LPS, proliferated and secreted the cytokines IL-6 and monocyte chemoattractant protein-1 (MCP-1). However, the TLR-responsiveness of CEC in IL-2¿/¿ mice was different with decreased TLR4 responsiveness and augmented TLR2 responses that result in IL-6 and MCP-1 secretion. TLR signaling in CEC did not involve NF-B (p65) activation with the inhibitory p50 form of NF-B predominating in CEC in both the healthy and inflamed colon. Development of colitis was, however, associated with the activation of MAPK family members and upregulation of MyD88-independent signaling pathways characterized by increased caspase-1 activity and IL-18 production. These findings identify changes in TLR expression and signaling during the development of colitis that may contribute to changes in the host response to bacterial antigens seen in colitis.
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Singh, J.C.I., Cruickshank, S.M., Newton, D.J. et al. (2004). Toll-like receptor-mediated responses of primary intestinal epithelial cells during the development of colitis. American Journal of Physiology Gastrointestinal and Liver Physiology. Vol. 288, No. 3, G514-G524.
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