Suzuki, Yasuo; Yamada, Akihiro; Aoki, Hiroshi; Osamura, Aisaku; Nakamura, Kentaro; Yoshimatsu, Yasushi; Hosoe, Nobuo; Takada, Nobuo; Tsuda, Yukio; Shirai, Koji (2008). W1254 The Decreased TLR2 Expression and Elevated IL-8 Production On Peripheral Leukocytes in Patients with Active Ulcerative Colitis: the Modulation of the Leukocyte Sensitivity to Pgn By Granulocyte and Monocyte Apheresis. Gastroenterology, 134(4), A-665–. doi:10.1016/S0016-5085(08)63105-4
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W1254 The Decreased TLR2 Expression and Elevated IL-8 Production On Peripheral Leukocytes in Patients with Active Ulcerative Colitis: the Modulation of the Leukocyte Sensitivity to Pgn By Granulocyte and Monocyte Apheresis
BACKGROUND & AIM: Mucosal lesions of active ulcerative colitis (UC) are characterized by acute inflammatory cell (polymorphonuclear granulocyte, PMN) infiltrate and ulceration. Granulocyte and monocyte apheresis (GMA) using a column device, Adacolumn, selectively adsorbs and removes leukocytes from the peripheral blood, and has been reported to be effective in patients with active UC. The aim of this study was to investigate the expression of toll like receptor 2 (TLR2) on PMNs and monocytes in patients with active UC as compared to the level in healthy subjects and see the impact of GMA on TLR2. METHODS: Fortyeight patients with active UC, Clinical Activity Index (CAI, Lichtiger index) ≥5, were included in this study. Patients received several GMA sessions (maximum 10 sessions), and CAI ≤ 3 was considered remission. Blood samples were obtained from patients at each GMA session and also from healthy subjects (n=14), after obtaining informed consent. The expression of TLR2 was investigated by flowcytometry. In several samples, IL-8 production by cultured blood upon stimulation with peptidoglycan (PGN, a ligand for TLR2) was measured (n=21). RESULTS: An average of CAI at the entry was 11.0 (n=48), and remission rate by GMA was 56.3%(27/48). At the baseline, the expression of TLR2 on PMN of patients with active UC was significantly less than the level in healthy subjects (p<0.001). Further, the improvement in CAI was accompanied by a trend towards normalization of TLR2 on PMN (up-regulation, p<0.05) together with a significant fall (P<0.01) of plasma IL-8 level. However, as for the patients with still active symptoms (CAI>5) in course of GMA therapy, the decreased TLR2 on PMN and the elevated release of IL-8 from PGN-stimulated leukocytes were kept on. By exposing blood to the column carriers In Vitro, TLR2 expression on the cell surface of PMN was decreased, but increased within the cellular of PMN. Similarly, in the blood on column outflow of GMA, the TLR2 expression on PMN and IL-8 production by PGN-stimulation were significantly decreased (TLR2:P<0.001, IL-8:P<0.001), indicating that leukocyte sensitivity to PGN is weakened by GMA column. CONCLUSION: The expression of TLR2 on PMN in patients with active UC is significantly decreased compared with remission status or healthy subjects. In connection with the decreased TLR2 expression, the IL-8 production by PGN-stimulated leukocytes is elevated in patients with active UC. These changes seem to reflect PMN activation based on UC disease activity. GMA or exposure of blood to GMA carriers is associated with down-modulation of the TLR2 expression on PMN and also leukocyte sensitivity to PGN
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