Mechanism Of Signal Molecule High Mobility Group Box Protein 1 Mediated By Toll-like Receptor 2 In Murine Asthma

Background Bronchial asthma(hereinafter referred to as asthma) is a chronic airway inflammatory diseases, and many cells and cellular components involved in it. Along with the industrialized extensive, asthma has become the main disease in most industrialized countries, which is seriously harm to human health. The main feature of asthma is chronic airway inflammation, airway hyperresponsiveness and airway reconstruction, the cytokines is critical in the pathophysiological process of asthma. Researches show that, high mobility group protein 1(HMGB1) is higher expression in serum and induce sputum of asthma patients. HMGB1 is an important cytokine that can regulate immune, and it has the function of inflammatory medium and tissue repair. HMGB1 that released into the extracellular is an important proinflammatory cytokine, playing an important role in the process of local and systemic inflammatory disease. Toll-like receptor(TLR), a kind of innate immune receptor, plays an important role in the innate immunity and the adaptive immunity and involves in the progress of pulmonary inflammatory disease, through identifying and combinding with many ligands involved in the progress of pulmonary inflammatory disease. TLR2 is the main pattern recognition receptor that identificate the components of mycobacterium cell wall, HMGB1 can be used as a kind of endogenous immune adjuvant, participating in immune response in a variety of diseases that mediated by TLR2, and promote the inflammation happening of airway.Objective To explore the role and mechanism of signal molecule high mobility group box protein1(HMGB1) mediated by Toll-like receptor 2(TLR2) in asthma.Methods Fourteen specific pathogen free(SPF) female C57 mice and TLR2-/- mice each were randomly divided into four groups of C57 control, C57 asthma, TLR2-/- control and TLR2-/- asthma( n=7 each). The animals were sensitized and challenged with ovalbumin(OVA) for asthmatic modeling. The same amount of normal saline was used in the control group. The supernatant of bronchoalveolar lavage fluid(BALF) was collected for detecting the level of HMGB1 by enzyme-linked immunosorbent assay(ELISA).And the expression of HMGB1 in lung tissue was detected by Western blott and immunohistochemistry.Results 1. Asthmatic murine model was successfully established:Mice irritability obviously, breathing deeply and fast and other performance after OVA atomization. 2. The level of HMGB1 in the BALF of C57 asthma group was significantly higher than that in C57 control, TLR2-/- asthma and TLR2-/- control groups((59.0±13.9) vs(42.3±1.6),(47.5±2.3),(42.4±1.4) ng/L; P=0.001, 0.001,0.037). 3. The results of immunohistochemistry showed that the marker of HMGB1 in lung tissue was less than those in the C57 control and TLR2-/- control groups. However, the C57 asthma and TLR2-/- asthma groups were obviously more and they were located in airway epithelium. 4. Western Blot showed that the expression of HMGB1 was significantly higher in C57 asthma group than that in the C57 control, TLR2-/- asthma and TLR2-/- control groups(0.92±0.29 vs 0.18±0.09, 0.31±0.16, 0.21±0.14; P=0.007, 0.022, 0.009).Conclusion HMGB1 promotes the airway inflammation mediated by TLR2. And it may participate in the pathogenesis of asthma.