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A novel anti-histone H1 monoclonal antibody, SSV monoclonal antibody, improves lung injury and survival in a mouse model of lipopolysaccharide-induced sepsis-like syndrome.
Kusano, Toru; Chiang, Kuei-Chen; Inomata, Masafumi; Shimada, Yayoi; Ohmori, Naoya; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Nakano, Toshiaki; Kawamoto, Seiji; Takaoka, Yuki; Shiraishi, Norio; Noguchi, Takayuki; Kitano, Seigo.
Afiliación
  • Kusano T; Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Hasama-machi, Yufu, Oita 879-5593, Japan.
  • Chiang KC; Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
  • Inomata M; Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Hasama-machi, Yufu, Oita 879-5593, Japan.
  • Shimada Y; Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
  • Ohmori N; Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
  • Goto T; Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
  • Sato S; Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
  • Goto S; Iwao Hospital, Yufuin 879-5102, Japan ; Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
  • Nakano T; Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
  • Kawamoto S; Department of Molecular Biotechnology, Graduate School of Advanced Science of Matter, Hiroshima University, Higashi-Hiroshima 739-8511, Japan.
  • Takaoka Y; Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
  • Shiraishi N; Center for Community Medicine, Oita University Faculty of Medicine, Oita 879-5593, Japan.
  • Noguchi T; Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita 879-5593, Japan.
  • Kitano S; Oita University, Oita 870-1192, Japan.
Biomed Res Int ; 2015: 491649, 2015.
Article en En | MEDLINE | ID: mdl-25649890
ABSTRACT

BACKGROUND:

Histones play important roles in both host defenses and inflammation related to microbial infection. A peptide mimotope (SSV) was identified from a novel histone H1 monoclonal antibody (16G9 mAb) that was shown to inhibit the mixed lymphocyte reaction. In the present study, an anti-SSV producing hybridoma was established. We investigated the effects of SSV mAb in a mouse acute inflammation model induced by intraperitoneal injection of lipopolysaccharide (LPS).

METHODS:

SSV mAb was generated and characterized. Mice were treated with SSV mAb or a control IgG antibody prior to LPS injection. Evaluation of survival rate and lung tissue on histological score was performed. The levels of inflammatory cytokines and histones H1, H3, and H4 in plasma and lung tissue were measured by ELISA.

RESULTS:

Competitive ELISA revealed that SSV mAb binds to histone H1. SSV mAb improved lung injury and prolonged the survival of LPS-injected mice. Increased levels of histones H1, H3, and H4 and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in plasma and lung tissue after LPS injection were ameliorated by SSV mAb.

CONCLUSION:

SSV mAb is shown to have anti-inflammatory activity and organ-protective effects, highlighting the importance of controlling histone H1 as well as H3 and H4 levels during inflammation.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Neumonía / Histonas / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomed Res Int Año: 2015 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Neumonía / Histonas / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomed Res Int Año: 2015 Tipo del documento: Article País de afiliación: Japón