caa a22 4500 445885173 CHVBK 20180317145557.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00011-011-0348-z doi (NATIONALLICENCE)springer-10.1007/s00011-011-0348-z Inhibition of macrophage activation and suppression of graft rejection by DTCM-glutarimide, a novel piperidine derived from the antibiotic 9-methylstreptimidone [Elektronische Daten] [Masatoshi Takeiri, Miyuki Tachibana, Ayumi Kaneda, Ayumi Ito, Yuichi Ishikawa, Shigeru Nishiyama, Ryoichi Goto, Kenichiro Yamashita, Susumu Shibasaki, Gentaro Hirokata, Michitaka Ozaki, Satoru Todo, Kazuo Umezawa] Objective: We have previously synthesized a novel piperidine compound, 3-[(dodecylthiocarbonyl)methyl]glutarimide (DTCM-glutarimide), that inhibits LPS-induced NO production, and in the present research we studied further the anti-inflammatory activity of DTCM-glutarimide in a macrophage cell line and in mice bearing transplanted hearts. Materials and methods: Mouse macrophage-like RAW264.7 cells were employed for the evaluation of cellular inflammatory activity. DTCM-glutarimide was synthesized in our laboratory. The AP-1 activity was measured by nuclear translocation and phosphorylation. For the heart transplantation experiment, male C57BL/6 (H-2b) and BALB/c (H-2d) mice were used as donor and recipient, respectively. DTCM-glutarimide was administered intraperitoneally. Results: DTCM-glutarimide inhibited the LPS-induced expression of iNOS and COX-2 in macrophages; but, unexpectedly, it did not inhibit LPS-induced NF-κB activation. Instead, it inhibited the nuclear translocation of both c-Jun and c-Fos. It also inhibited LPS-induced c-Jun phosphorylation. Moreover, it inhibited the mixed lymphocyte reaction in primary cultures of mouse spleen cells; and furthermore, in mice it prolonged the graft survival in heart transplantation experiments. Conclusion: The novel piperidine compound, DTCM-glutarimide, was found to be a new inhibitor of macrophage activation, inhibiting AP-1 activity. It also inhibited graft rejection in mice, and thus may be a candidate for an anti-inflammatory agent. Springer Basel AG, 2011 DTCM-glutarimide nationallicence LPS nationallicence AP-1 nationallicence Mixed lymphocyte reaction nationallicence Heart transplantation nationallicence Takeiri Masatoshi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut Tachibana Miyuki Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut Kaneda Ayumi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut Ito Ayumi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut Ishikawa Yuichi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut Nishiyama Shigeru Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut Goto Ryoichi Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut Yamashita Kenichiro Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut Shibasaki Susumu Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut Hirokata Gentaro Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut Ozaki Michitaka Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut Todo Satoru Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut Umezawa Kazuo Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut Inflammation Research SP Birkhäuser Verlag Basel 60/9(2011-09-01), 879-888 1023-3830 60:9<879 2011 60 11 https://doi.org/10.1007/s00011-011-0348-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0348-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takeiri Masatoshi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut NATIONALLICENCE 700 1- Tachibana Miyuki Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut NATIONALLICENCE 700 1- Kaneda Ayumi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut NATIONALLICENCE 700 1- Ito Ayumi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut NATIONALLICENCE 700 1- Ishikawa Yuichi Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut NATIONALLICENCE 700 1- Nishiyama Shigeru Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut NATIONALLICENCE 700 1- Goto Ryoichi Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut NATIONALLICENCE 700 1- Yamashita Kenichiro Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut NATIONALLICENCE 700 1- Shibasaki Susumu Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut NATIONALLICENCE 700 1- Hirokata Gentaro Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut NATIONALLICENCE 700 1- Ozaki Michitaka Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut NATIONALLICENCE 700 1- Todo Satoru Department of Surgery, Hokkaido University School of Medicine, 060-8683, Sapporo, Japan aut NATIONALLICENCE 700 1- Umezawa Kazuo Center for Chemical Biology, School of Fundamental Science and Technology, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, 223-0061, Yokohama, Japan aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/9(2011-09-01), 879-888 1023-3830 60:9<879 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer