title: Impact of Histone H1 on the Progression of Allergic Rhinitis and Its Suppression by Neutralizing Antibody in Mice.
abstract: Nuclear antigens are known to trigger off innate and adaptive immune responses. Recent studies have found that the complex of nucleic acids and core histones that are derived from damaged cells may regulate allergic responses. However, no fundamental study has been performed concerning the role of linker histone H1 in mast cell-mediated type I hyperreactivity. In this study, we explored the impact of histone H1 on mast cell-mediated allergic responses both in vitro and in vivo. In the course of a bona-fide experimental allergen sensitization model upon co-injection with alum adjuvant, ovalbumin (OVA), but not PBS, induced elevated levels of circulating histone H1. Intranasal challenge with histone H1 to OVA/alum- (but not PBS/alum)-sensitized mice induced significantly severer symptoms of allergic rhinitis than those in mice sensitized and challenged with OVA. A monoclonal antibody against histone H1 not only suppressed mast cell degranulation, but also ameliorated OVA-induced nasal hyperreactivity and IgE-mediated passive cutaneous anaphylaxis. Our present data suggest that nuclear histone H1 represents an alarmin-like endogenous mediator acting on mast cells, and that its blockage has a therapeutic potential for mast cell-mediated type I hyperreactivity.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Liver Transplantation Center and Division of Transplant Immunology, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Kamei
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Liver Transplantation Center and Division of Transplant Immunology, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Center for Gene Science, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takaoka
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Ayane
authors.initials: A
authors.lastname: Hori
authors.affiliation: Liver Transplantation Center and Division of Transplant Immunology, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Kazusa Institute for Drug Discovery, Josai International University, Kisarazu, Japan.
authors.forename: Kuei-Chen
authors.initials: KC
authors.lastname: Chiang
authors.affiliation: Kazusa Institute for Drug Discovery, Josai International University, Kisarazu, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Kazusa Institute for Drug Discovery, Josai International University, Kisarazu, Japan.|Basic Medical Science of Nursing, Faculty of Nursing, Department of Nursing, Josai International University, Togane, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohmori
authors.affiliation: Kazusa Institute for Drug Discovery, Josai International University, Kisarazu, Japan.|Basic Medical Science of Nursing, Faculty of Nursing, Department of Nursing, Josai International University, Togane, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.|Department of Food Sciences and Biotechnology, Faculty of Life Sciences, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ono
authors.affiliation: Liver Transplantation Center and Division of Transplant Immunology, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Liver Transplantation Center and Division of Transplant Immunology, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Basic Medical Science of Nursing, Faculty of Nursing, Department of Nursing, Josai International University, Togane, Japan.|Fukuoka Institution of Occupational Health, Fukuoka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawamoto
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006657:Histones / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E; D008297:Male; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D065631:Rhinitis, Allergic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000485:Allergens; D057134:Antibodies, Neutralizing; D006657:Histones; D010446:Peptide Fragments; D007073:Immunoglobulin E; D010047:Ovalbumin