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Background and objective Repeated inhalation of sevoflurane ( SVF) can benefit asthmatic patients by bronchodilation. However, the impact of repeated inhalation of SVF on allergic airway inflammation has not been clarified. This study was aimed at investigating the effects of repeated inhalation of SVF on airway inflammation in mice. Methods Female C57BL/6 mice were sensitized with ovalbumin ( OVA) and treated by inhalation with SVF or vehicle daily for seven consecutive days, immediately followed by OVA challenge. Airway inflammation was evaluated by counting the numbers of different types of inflammatory infiltrates in bronchoalveolar lavage fluid ( BALF), histology, cytokine measurements and mucus production in individual mice. Results In comparison with the OVA group, repeated inhalation of SVF significantly reduced the numbers of total cells, eosinophils, lymphocytes, macrophages and neutrophils ( P < 0.05 to P < 0.01), and the levels of BALF tumour necrosis factor-α and lung high-mobility group box 1 ( P < 0.01), accompanied by elevated levels of BALF interleukin-10 in allergic mice ( P < 0.05). Repeat inhalation of SVF decreased the levels of serum OVA-specific immunoglobulin E ( IgE) and mitigated allergic airway epithelial goblet cell hyperplasia and mucus hypersecretion in allergic mice ( P < 0.01). Conclusions Repeated inhalation of SVF inhibits allergic airway inflammation by reducing inflammatory infiltrates, improving the imbalance of cytokine responses and mitigating allergen-specific IgE responses and goblet cell hyperplasia in mice. [ABSTRACT FROM AUTHOR]

Activation of toll-like receptor (TLR) signaling that initiates an innate immune response to pathogens must be strictly regulated to prevent excessive inflammatory damage in the host. Here, we demonstrate that Mer receptor tyrosine kinase (MerTK) is a negative regulatory molecule in the lipoteichoic acid (LTA)-induced inflammatory response. LTA that activated TLR2 signaling concomitantly induced activation of MerTK signaling in RAW264.7 macrophages, including phosphoinositide 3-kinase (PI3K)/Akt and suppressor of cytokine signaling 3 (SOCS3). Moreover, LTA induced MerTK activation in a time-dependent manner, and LTA-induced MerTK activation was dependent on the ligand Gas6. Additionally, pretreatment with a specific Mer-blocking antibody significantly inhibited LTA-induced phosphorylation of MerTK, while further enhancing LTA-induced phosphorylation of IκB-α and NF-κBp65 as well as production of TNF-α and IL-6. Meanwhile, the antibody blockade of MerTK markedly prevented LTA-induced Akt phosphorylation and SOCS3 expression, both of which were crucial for the inhibition of TLR2-mediated immune response. Collectively, these results suggest, for the first time, that MerTK is an intracellular negative feedback regulator that inhibits the inflammatory response of LTA-stimulated macrophages through the PI3K/Akt pathway and SOCS3 protein. [ABSTRACT FROM AUTHOR]