Yong Chen1, Shaoyong Liang2, Feiwu Long2, Jinzheng Li2, Jianping Gong3. 1. Department of Hepatobiliary Surgery, First Affiliated Hospital, Chongqing Medical University, Linjiang Road 76#, Chongqing, 400010, People's Republic of China; Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Linjiang Road 76#, Chongqing, 400010, People's Republic of China. 2. Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Linjiang Road 76#, Chongqing, 400010, People's Republic of China. 3. Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Linjiang Road 76#, Chongqing, 400010, People's Republic of China. Electronic address: gongjianping11@126.com.
Abstract
BACKGROUND: The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. METHODS: Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 μg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of (3)H-thymidine TCs. RESULTS: (1) Treatment with ALR significantly decreased interleukin-2 and interferon-γ expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-α expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. CONCLUSIONS: ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation.
BACKGROUND: The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. METHODS: Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 μg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of (3)H-thymidine TCs. RESULTS: (1) Treatment with ALR significantly decreased interleukin-2 and interferon-γ expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-α expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. CONCLUSIONS:ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation.
Authors: Thomas S Weiss; Madeleine Lupke; Rania Dayoub; Edward K Geissler; Hans J Schlitt; Michael Melter; Elke Eggenhofer Journal: Cells Date: 2019-11-12 Impact factor: 6.600