title: A nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates GVHD in allogeneic bone marrow transplantation.
abstract: GVHD is a crucial mortality factor in allogeneic bone marrow transplantation (ABMT). In this paper, we show that dehydroxymethylepoxyquinomicin (DHMEQ), a novel inhibitor of nuclear factor-κB, suppresses GVHD, resulting in an improved mortality rate in a mouse ABMT model. Bone marrow cells from C57BL/6 mice (B6 mice) were transplanted into lethally irradiated BALB/c mice. Two weeks later, spleen cells from B6 mice were transplanted into the irradiated BALB/c mice. From one week after the injection of spleen cells, when the mice started to show GVHD, the mice were also injected intraperitoneally daily with DHMEQ or vehicle only (DMSO) for 4 weeks. By 80 days after the ABMT, 6/14 of the vehicle-injected mice (43%) had died because of GVHD, whereas all DHMEQ-injected mice survived this observation period and developed milder GVHD than the vehicle-injected mice. When regulatory T cells were reduced by the injection of anti-folate receptor 4 (FR4) antibody, the effects of DHMEQ were reduced. These findings suggest that administration of DHMEQ could become a new strategy for preventing fatalities from GVHD.
authors.affiliation: Department of Pediatrics, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan.
authors.forename: Sohsaku
authors.initials: S
authors.lastname: Yamanouchi
authors.affiliation: Division of Surgical Pathology, Toyooka Hospital, Toyooka City, Hyogo 668-8501, Japan; Department of Stem Cell Disorders, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan. Electronic address: adachiya250@gmail.com.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.affiliation: Department of Pediatrics, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Shimo
authors.affiliation: Department of Molecular Target Medicine Screening, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Department of Internal Medicine, Otokoyama Hospital, Yawata City, Kyoto 614-8366, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Okigaki
authors.affiliation: Department of Pediatrics, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Takaya
authors.affiliation: Department of Clinical Laboratory, Toyooka Hospital, Tobera, Toyooka City, Hyogo 668-8501, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kuge
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
authors.affiliation: Department of Pediatrics, Kansai Medical University, Hirakata City, Osaka 573-1010, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001549:Benzamides / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000187:drug effects; D003512:Cyclohexanones / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D001549:Benzamides; D003512:Cyclohexanones; D016207:Cytokines; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C464444:dehydroxymethylepoxyquinomicin; C543634:folate receptor 4, mouse
keywords: Allogeneic bone marrow transplantation; Dehydroxymethylepoxyquinomicin (DHMEQ); Graft versus host disease; NF-κB; Regulatory T cell; Survival rate