Denatonium benzoate promotes IgE-mediated mast celldegranulation and ovalbumin-induced allergic diarrheain BALB/c mice
Ju Liu,1† Huaping Xu,2† Shaotong Feng,1 Xiaoyun Shi,3 Xin Li,4 Jiexin Zou,1 Linbo Shi1
Affiliations:
1 School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
2 Department of Rehabilitation, First Affiliated Hospital of Nanchang University, Nanchang, China
3 Department of Anesthesiology, First Affiliated Hospital of Nanchang University, Nanchang, China
4 School of Food Science and Technology, Nanchang University, Nanchang, China
† Ju Liu and Huaping Xu contributed equally to this work and should be considered co-authors.
Abstract
Background: Denatonium benzoate (DB), one of the most bitter compounds known to man, is used for alcohol denaturation. Some reports have demonstrated that asthmatic symptoms are associated with DB exposure, but the possible links between DB and immunoglobulin E (IgE)-mediated allergy susceptibility have not yet been examined.
Objective: This study investigated the effects of DB on in vitro IgE-mediated mast cell degranulation and food allergy in BALB/c mice.
Methods: IgE-sensitized rat RBL-2H3 cells (a basophilic leukemia mast cell line) and human KU812 cells (a basophilic cell line) and mice with ovalbumin (OVA)-induced allergy were treated with DB. Histamine release, calcium ion (Ca2+) influx, phosphorylated spleen tyrosine kinase (p-Lyn) and phosphorylated phospholipase C-γ (p-PLCγ) levels, OVA-specific IgE, anaphylactic symptoms, and the cell-surface expression of the high-affinity IgE receptor α-subunit (FcεRIα) on mast cells were evaluated.
Results: DB increased histamine release, Ca2+ mobilization, and p-Lyn and p-PLCγ levels in IgE-mediated activated RBL-2H3 and KU812 cells, and enhanced the cell-surface expression of FcεRIα messenger RNA (mRNA). In mice, DB increased the severity of OVA-induced anaphylactic and diarrheic symptoms, the mucus thickness in the jejunum, histamine and OVA-specific IgE levels, and FcεRIα mRNA in isolated mucosal mast cells.
Conclusion: Our work indicates that DB promotes IgE-mediated mast cell degranulation and OVA-induced allergic diarrhea in BALB/c mice, providing evidence that exposure to DB promotes allergy susceptibility.
Key words: Denatonium benzoate, IgE, FcεRIα, mast cell degranulation, allergic diarrhea