The Role Of High Mobility Group Box 1 Protein In Murine Allergic Rhinitis And Acute Bacterial Rhinosinusitis

Part Ⅰ Altered expression and location of HMGB1 and activation of inflammasomes in nasal mucosa of murine allergic rhinitis and acute bacterial rhinosinusitisObjective:To study altered expression and location of HMGB1 and activation of inflammasomes using murine allergic rhinitis and acute bacterial rhinosinusitis model.Methods:Twenty Balb/c mice were recruited for experiment. The mice were injected intraperitoneally on the first, eighth, and 15th days of the study with a solution consisting of 40 mg OVA dissolved in 200 ml PBS which was emulsified with 2mg aluminum hydroxide. The OVA challenges were performed daily by intranasal instillation with 500 mg OVA in 20 ml PBS into the bilateral nasal cavity from the 22nd day and lasted for one week. After last intranasal administration, the number of sneezes and the nasal rubbings of each mouse was counted for 10 min by blinded observers.24 hours after last chanllenge, nasal lavage fluid and nasal mucasao were collected for further analysis. Twenty C57BL/6 were enroll in the experiment.40μl lipopolysaccharides dissolved in 40μl PBS was intranasal instillated into the bilateral nasal cavity. The samples were harvested at 4th day after nasal chanllenge. The expression of Nlrp3, AIM2, Asc, caspase-1, and HMGB1 were detected by Western Blot and immunohistochemistry. HE staining was also performed.Results:Eosinophils infiltration was found in nasal mucosa of AR mouse, and the level of IgE in serum was elevated. Large amounts of neutrophils were found in the sinus of ABRS mouse. The expression of components of AIM2 inflammasome e.g AIM, Asc, caspase-1 p20 but not Nlrp3 were increased in AR mice, whereas Nlrp3 inflammasome was activated in ABRS mouse. TUNEL positive cells were increased in nasal mucosa and the cleavage of caspase-3 and PARP-1 was not found.Conclusion:The increased expression and translocation of HMGB1 was found in nasal mucosa of AR and ABRS mouse. AIM2 inflammasome and Nlrp3 inflammasome was activated in AR and ABRS mouse, respectively. The activation of inflammasome may contribute to the release of HMGB1.Part Ⅱ Ethyl pyruvate attenuates murine allergic rhinitis and acute bacterial rhinosinusitis by decreasing HMGB1 release.Objective:To observe the effect of ethyl pyruvate on murine allergic rhinitis and acute bacterial rhinosinusitisMethods:Murine AR and ABRS model were established as Part Ⅰ. The mice in the EP administration group were given an intraperitoneal injection of EP 30 min before OVA or LPS treatment. The inflammatory cells infiltration was observed by HE staining, The number of nasal rubbings and sneezes of each mouse was counted after final treatment. AB-PAS staining, interleukin-4 and 13 in NLF, IgE, and the protein expression of HMGB1 were measured. OVA-specific IgE, IgG2a and IgG1 were also measured by ELISA. The expression of TLR4 and NF-κB in ABRS mouse were detected by Western Blot and immunohistochemistry.Result:Th-2 cytokine production, total IgE, and goblet cell hyperplasia were significantly inhibited by treatment with EP. The expression and release of HMGB1 were reduced by EP in a dose-dependent manner. EP has no impact on OVA-specific IgG2a and IgGl. Large amounts of neutrophils were found in the sinus of ABRS mouse, and neutrophils infiltration was decreased after EP adminstration. The expression of TLR4 and NF-κB were significantly increased in nasal mucosa of ABRS mouse, and EP suppressed the expression of TLR4 and NF-κB. HMGB1 was released in nasal mucosa of ABRS mouse and EP decreased the translocation of HMGB1.Conclusion:Ethyl pyruvate attenuates murine allergic rhinitis and acute bacterial rhinosinusitis through decreasing HMGB1 expression and release.