High mobility group box 1 (HMGB1) is a DNA-binding protein that is abundantly expressed in most tissues. Recently, HMGB1 has gained much attention for its regulation of immunity and inflammation. Yet its role in toluene diisocyanate (TDI)-induced asthma still remains poorly characterized. In this study, mice were sensitized and challenged with TDI to establish a TDI-induced asthma model. An IgY anti-HMGB1 antibody or isotype IgY was given intraperitoneally after each challenge. Airway reactivity to methacholine, airway inflammation, bronchial epithelial hyperplasia and shedding were unexpectedly aggravated after administration of the anti-HMGB1 antibody and was accompanied by increased pulmonary expression of HMGB1, especially in those mice treated with IgY. Levels of IL-4, IL-5, IL-13 and TNF-α were also elevated with TDI-induction. Primary lymphocytes from TDI sensitized and challenged mice demonstrated increased secretion of IL-4 after IgY stimulation. To confirm the effect of IgY, a cohort of mice exposed to TDI or vehicle was injected with IgY and the same results were observed after IgY treatment as in TDI asthmatic mice. Taken together, these results show that the IgY anti-HMGB1 antibody can facilitate TDI-induced allergic airway inflammation. Specifically, IgY, rather than anti-HMGB1, plays an important role in the process of exacerbated asthma, shedding light on an underappreciated role of avian IgY.
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Airway inflammation; Asthma; IgY anti-HMGB1; Toluene diisocyanate