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Background: Our colleagues have demonstrated an impressive therapeutic role of sevoflurane in a murine allergic airway inflammation model, but the mechanisms underlying this effect remain undefined. In this study, we tried to investigate the effect of sevoflurane on the resolution of allergic airway inflammation and to assess whether NLRP3 or the NLRP3 inflammasome is involved in this process.Methods: Female (C57BL/6) mice were sensitized and challenged with ovalbumin (OVA). Then, some of the mice received MCC950 (10 mg/kg; i.p.) or 3% sevoflurane. Total and differential inflammatory cell numbers, proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), the peribronchial inflammation density, and mucus production were evaluated. In addition, we analysed the protein levels of NLRP3, the apoptosis-associated speck-like protein containing the caspase activation and recruitment domain (ASC), pro-caspase-1, and caspase-1 in the lung tissue.Results: We found that OVA-induced inflammatory cell recruitment to peribronchial regions, goblet cell hyperplasia, the serum levels of IgE, inflammatory cells, and the Th2 cytokine secretion in BALF was potently suppressed by sevoflurane with an efficacy comparable with that suppressed by MCC950 treatment. Furthermore, sevoflurane, similar to MCC950, clearly inhibited the OVA-induced activity of NLRP3 in the lungs. In addition, we found that OVA challenge failed to increase the expression of ASC, pro-caspase-1, and caspase-1 in the lungs and the levels of IL-18 and IL-1β in BALF.Conclusion: Taken together, our data showed that sevoflurane ameliorated allergic airway inflammation by inhibiting Th2 responses and NLRP3 expression. The NLRP3 independent of inflammasomes participated in the pathogenesis of allergic asthma in this model. [ABSTRACT FROM AUTHOR]

Nebulized lidocaine has been suggested to be beneficial in asthma therapy, but the underlying mechanisms are little known. We aimed to investigate whether Toll-like receptor (TLR) 2 was involved in the protective effect of lidocaine on allergic airway inflammation. Female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). Meanwhile, some of the mice were treated with TLR2 agonist (Pam3CSK4, 100 μg) intraperitoneally in combination with OVA on day 0. Just after allergen provocation, mice were treated with inhaled lidocaine or vehicle for 30 min. In this model, we found that lidocaine markedly attenuated OVA-evoked airway inflammation, leukocyte recruitment and mucus production. Moreover, lidocaine abrogated the increased concentrations of T cytokines and TNF-α in bronchoalveolar lavage fluid (BALF) of allergic mice, as well as reducing the expression of phosphorylated nuclear factor (P-NF)-κBp65 and the NOD-like receptor pyridine containing 3 (NLRP3), which are important for the production of pro-inflammatory cytokines. In addition, our study showed that lidocaine dramatically decreased OVA-induced increased expression of TLR2 in the lung tissues. Furthermore, activation of TLR2 aggravated OVA-challenged airway inflammation, meanwhile, it also elevated OVA-induced expression of P-NF-κBp65 and NLRP3 in the lungs. However, lidocaine effectively inhibited airway inflammation and counteracted the expression of P-NF-κBp65 and NLRP3 in allergic mice pretreated with Pam3CSK4. Taken together, the present study demonstrated that lidocaine prevented allergic airway inflammation via TLR2 in an OVA-induced murine allergic airway inflammation model. TLR2/NF-κB/NLRP3 pathway may serve as a promising therapeutic strategy for allergic airway inflammation. [ABSTRACT FROM AUTHOR]