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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

Induction of circulating histone H1 by OVA/alum sensitization and its correlation with OVA-specific IgE production.Circulating histone H1 (A) and OVA-specific IgE (B) levels were measured by ELISA. **, P<0.01 versus the pre-immunized serum. NS: not significant.
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pone.0153630.g001: Induction of circulating histone H1 by OVA/alum sensitization and its correlation with OVA-specific IgE production.Circulating histone H1 (A) and OVA-specific IgE (B) levels were measured by ELISA. **, P<0.01 versus the pre-immunized serum. NS: not significant.

Mentions: To explore the fundamental role of histone H1 in the course of allergen sensitization in vivo, the serum levels of histone H1 before and after OVA sensitization were evaluated. As shown in Fig 1A, OVA/alum-sensitized mice (n = 12) expressed significantly higher levels of histone H1 in the serum. The total (S1 Fig) and OVA-specific IgE levels were also elevated after OVA/alum sensitization (Fig 1B). However, PBS/alum sensitization (n = 6) failed to elevate either the histone H1 or total/OVA-specific IgE levels (Fig 1A and 1B). These results suggest the significance of OVA/alum sensitization in the activation of proinflammatory immune responses, resulting in the elevation of both the total/OVA-specific IgE and circulating histone H1 levels in vivo.


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)

Induction of circulating histone H1 by OVA/alum sensitization and its correlation with OVA-specific IgE production.Circulating histone H1 (A) and OVA-specific IgE (B) levels were measured by ELISA. **, P<0.01 versus the pre-immunized serum. NS: not significant.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153630.g001: Induction of circulating histone H1 by OVA/alum sensitization and its correlation with OVA-specific IgE production.Circulating histone H1 (A) and OVA-specific IgE (B) levels were measured by ELISA. **, P<0.01 versus the pre-immunized serum. NS: not significant.
Mentions: To explore the fundamental role of histone H1 in the course of allergen sensitization in vivo, the serum levels of histone H1 before and after OVA sensitization were evaluated. As shown in Fig 1A, OVA/alum-sensitized mice (n = 12) expressed significantly higher levels of histone H1 in the serum. The total (S1 Fig) and OVA-specific IgE levels were also elevated after OVA/alum sensitization (Fig 1B). However, PBS/alum sensitization (n = 6) failed to elevate either the histone H1 or total/OVA-specific IgE levels (Fig 1A and 1B). These results suggest the significance of OVA/alum sensitization in the activation of proinflammatory immune responses, resulting in the elevation of both the total/OVA-specific IgE and circulating histone H1 levels in vivo.

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