Original Article
High mobility group box 1: a novel mediator of Th2-type response-induced airway inflammation of acute allergic asthma
Abstract
Background: High mobility group box 1 (HMGB1) is an inflammatory mediator involved into the advanced stage of systemic inflammatory response syndrome (SIRS), and is over-expressed in bacterial sepsis and hemorrhagic shock. Recently, it has been found that the HMGB1 was abnormally expressed in induced sputum and plasma of asthmatic patients. However, the precise role of HMGB1 in the acute allergic asthma is unclear. Therefore, we aim to investigate the role HMGB1 in regulating airway inflammation of acute allergic asthma and its possible mechanism in this study.
Methods: Forty-eight BALB/c female mice were randomly divided into four groups: control group (Control), asthma group (Asthma), HMGB1 group (HMGB1) and anti-HMGB1 (HMGB1 monoclonal antibody of mice) group (Anti-HMGB1). Acute allergic asthma mice models were established by ovalbumin (OVA)-challenge. Then, we measured the levels of HMGB1 in bronchoalveolar lavage fluid (BALF) and lung tissue of mice. Finally, after exogenous HMGB1 and/or anti-HMGB1 administration, pulmonary function test, histological analysis, Western blot, cytological analysis and ELISA assay were performed to explore the effect of HMGB1 in acute allergic asthma.
Results: The levels of HMGB1 in BALF and lung tissue and the expression of HMGB1 protein in the lung tissue of asthma group were significantly higher than those in control group, respectively (P<0.01). Moreover, the HMGB1 group was showed an increased mucus secretion and infiltration of eosinophils and neutrophils in the airway of asthma mice, and a decrease of pulmonary function, compared to control group (P<0.01, respectively). Meanwhile, exogenous HMGB1 could increase the levels of IL-4, IL-5, IL-6, IL-8 and IL-17, whereas could reduce the IFN-γ in the BALF and lung tissue (P<0.05, respectively). Exogenous HMGB1 could enhance GATA3 expression of Th2 cells and attenuate the T-bet expression of Th1 cells (P<0.05, respectively), which could be abrogated after inhibiting HMGB1.
Conclusions: HMGB1 could aggravate eosinophilic inflammation in the airway of acute allergic asthma through inducing a dominance of Th2-type response and promoting the neutrophilic inflammation.
Methods: Forty-eight BALB/c female mice were randomly divided into four groups: control group (Control), asthma group (Asthma), HMGB1 group (HMGB1) and anti-HMGB1 (HMGB1 monoclonal antibody of mice) group (Anti-HMGB1). Acute allergic asthma mice models were established by ovalbumin (OVA)-challenge. Then, we measured the levels of HMGB1 in bronchoalveolar lavage fluid (BALF) and lung tissue of mice. Finally, after exogenous HMGB1 and/or anti-HMGB1 administration, pulmonary function test, histological analysis, Western blot, cytological analysis and ELISA assay were performed to explore the effect of HMGB1 in acute allergic asthma.
Results: The levels of HMGB1 in BALF and lung tissue and the expression of HMGB1 protein in the lung tissue of asthma group were significantly higher than those in control group, respectively (P<0.01). Moreover, the HMGB1 group was showed an increased mucus secretion and infiltration of eosinophils and neutrophils in the airway of asthma mice, and a decrease of pulmonary function, compared to control group (P<0.01, respectively). Meanwhile, exogenous HMGB1 could increase the levels of IL-4, IL-5, IL-6, IL-8 and IL-17, whereas could reduce the IFN-γ in the BALF and lung tissue (P<0.05, respectively). Exogenous HMGB1 could enhance GATA3 expression of Th2 cells and attenuate the T-bet expression of Th1 cells (P<0.05, respectively), which could be abrogated after inhibiting HMGB1.
Conclusions: HMGB1 could aggravate eosinophilic inflammation in the airway of acute allergic asthma through inducing a dominance of Th2-type response and promoting the neutrophilic inflammation.
