Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:"Legionella pneumophila induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages. | Morinaga et al. Respiratory Research 2010 11 158 http content 11 1 158 RESPIRATORY RESEARCH RESEARCH Open Access Legionella pneumophila induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages 2 1 2 Yoshitomo Morinaga 1 Katsunori Yanagihara 1 Shigeki Nakamura Hiroo Hasegawa Masafumi Seki 2 2 2 1 1 Koichi Izumikawa 1 Hiroshi Kakeya 1 Yoshihiro Yamamoto 1 Yasuaki Yamada 1 Shigeru Kohno 11 Shimeru Kamihira Abstract Background Legionella pneumophila LPN can cause a lethal infectious disease with a marked inflammatory response in humans. However the mechanism of this severe inflammation remains poorly understood. Since necrosis is known to induce inflammation1 we investigated whether LPN induces necrosis in macrophages. We also analyzed the involvement of lysosomal cathepsin B in LPN-induced cell death. Methods The human monocytic cell line THP-1 was infected with LPN1 NUL1 strain. MG132-treated cells were used as apoptotic control cells. After infection1 the type of cell death was analyzed by using microscopy1 LDH release and flow cytometry. As a proinflammatory mediator1 high-mobility group box 1 HMGB-1 Z was measured. Cathepsin B activity was also measured and the inhibitory effects of cathepsin B on LPN-induced cell death were analyzed. Results THP-1 cells after treatment with high dose of LPN showed necrotic features with releasing HMGB-1. This necrosis and the HMGB-1 release were inhibited by a specific lysosomal cathepsin B inhibitor and were characterized by a rapid and high activation of cathepsin B that was not observed in apoptotic control cells. The necrosis was also accompanied by cathepsin B-dependent poly ADP-ribose polymerase PARP cleavage. Conclusions We demonstrate here that L. pneumophila rapidly induces cathepsin B-dependent necrosis in a dosedependent manner and releases a proinflammatory mediator1 HMGB-k from macrophages. This report describes a novel aspect of the
