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Impact of Histone H1 on the Progression of Allergic Rhinitis and Its Suppression by Neutralizing Antibody in Mice.

Nakano T, Kamei R, Fujimura T, Takaoka Y, Hori A, Lai CY, Chiang KC, Shimada Y, Ohmori N, Goto T, Ono K, Chen CL, Goto S, Kawamoto S - PLoS ONE (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Cytokine release from total splenocytes stimulated with OVA.After the final OVA nasal challenge, the mice were sacrificed, and splenocytes were collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Splenocytes were stimulated with OVA for 72 hrs, and culture media were obtained. Cytokine levels (A: IFN-γ, B: IL-4, C: IL-5, D: IL-10, E: IL-13, and F: IL-17) were determined by using specific ELISA kits. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.
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pone.0153630.g007: Cytokine release from total splenocytes stimulated with OVA.After the final OVA nasal challenge, the mice were sacrificed, and splenocytes were collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Splenocytes were stimulated with OVA for 72 hrs, and culture media were obtained. Cytokine levels (A: IFN-γ, B: IL-4, C: IL-5, D: IL-10, E: IL-13, and F: IL-17) were determined by using specific ELISA kits. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.

Mentions: To explore the effect of SSV mAb on cytokine profiles, we next evaluated cytokine secretion after the OVA stimulation of splenocytes from OVA-sensitized and OVA-challenged mice. As shown in Fig 7, the IL-5 and IL-13 levels were slightly elevated by SSV mAb treatment, while the IFN-γ, IL-4, IL-10, and IL-17 levels showed no significant difference between SSV mAb- and isotype IgG1-treated mice.


Impact of Histone H1 on the Progression of Allergic Rhinitis and Its Suppression by Neutralizing Antibody in Mice.

Nakano T, Kamei R, Fujimura T, Takaoka Y, Hori A, Lai CY, Chiang KC, Shimada Y, Ohmori N, Goto T, Ono K, Chen CL, Goto S, Kawamoto S - PLoS ONE (2016)

Cytokine release from total splenocytes stimulated with OVA.After the final OVA nasal challenge, the mice were sacrificed, and splenocytes were collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Splenocytes were stimulated with OVA for 72 hrs, and culture media were obtained. Cytokine levels (A: IFN-γ, B: IL-4, C: IL-5, D: IL-10, E: IL-13, and F: IL-17) were determined by using specific ELISA kits. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835108&req=5

pone.0153630.g007: Cytokine release from total splenocytes stimulated with OVA.After the final OVA nasal challenge, the mice were sacrificed, and splenocytes were collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Splenocytes were stimulated with OVA for 72 hrs, and culture media were obtained. Cytokine levels (A: IFN-γ, B: IL-4, C: IL-5, D: IL-10, E: IL-13, and F: IL-17) were determined by using specific ELISA kits. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.
Mentions: To explore the effect of SSV mAb on cytokine profiles, we next evaluated cytokine secretion after the OVA stimulation of splenocytes from OVA-sensitized and OVA-challenged mice. As shown in Fig 7, the IL-5 and IL-13 levels were slightly elevated by SSV mAb treatment, while the IFN-γ, IL-4, IL-10, and IL-17 levels showed no significant difference between SSV mAb- and isotype IgG1-treated mice.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus